Appendix

In this Appendix biographical sketches are compiled of many scientists who have made notable contributions to the development of peptide chemistry up to its present state. We have tried to consider names mainly connected with important events during the earlier periods of peptide history, but could not include all authors mentioned in the text of this book. This is particularly true for the more recent decades when the number of peptide chemists and biologists increased to such an extent that their enumeration would have gone beyond the scope of this Appendix.

250 Appendix

Plate 8. Emil Abderhalden (1877-1950), Photo Plate 9. S. Akabori Leopoldina, Halle

J

Plate 10. Ernst Bayer Plate 11. Karel Blaha (1926-1988)

Appendix 251

Plate 12. Max Brenner Plate 13. Hans Brockmann (1903-1988)

Plate 14. Victor Bruckner (1900- 1980) Plate 15. Pehr V. Edman (1916- 1977)

252 Appendix

Plate 16. Lyman C. Craig (1906-1974)

Plate 17. Vittorio Erspamer Plate 18. Joseph S. Fruton, Biochemist and Historian

Plate 19. Rolf Geiger (1923-1988)

Plate 21. Dorothy Hodgkins

Appendix 253

Plate 20. Wolfgang Konig

Plate. 22. Franz Hofmeister (1850-1922), (Fischer, biograph. Lexikon)

254 Appendix

Plate 23. The picture shows the late Professor 1.E. Jorpes (r.j and Professor V. Mutt during their favorite pastime in the archipelago on the Baltic near Stockholm

Plate 24. Ephraim Katchalski (Katzir) Plate 25. Abraham Patchornik

Appendix 255

Plate 26. P.G. Katsoyannis Plate 27. George W. Kenner (1922-1978)

Plate 28. Edger Lederer (1908- 1988) Plate 29. Hennann Leuchs (1879-1945)

256 Appendix

Plate 30. Choh Hao Li (1913-1987) Plate 31. A.J.P. Martin

Plate 32. Miguel A. Ondetti Plate 33. Yuri A. Ovchinnikov (1934- 1988)

Appendix 257

Plate 34. Linus Pauling, 40 years a-Helix "We have now used this information (about interatomic distances, bond angles and other . .. [the author]) to construct two reason­able hydrogen-bonded helical configurations for the polypeptide chain; we think that it is likely that these configurations constitute an impor­tant part of the structure of both fibrous and globular proteins, as well as of synthetic poly­peptides". (From Linus Pauling, Robert B. Corey and H.R. Branson, The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain, Proc. NatL Acad. Sci. USA 37: 205-211, 1951)

Plate 35. Iphigenia Ph otaki (1921-1983) with Leonidas Zervas

258 Appendix

Plate 36. H. Norman Rydon Plate 37. Shumpei Sakakibara

Plate 38. Frederick Sanger Plate 39. Robert Schwyzer

Appendix 259

Plate 40. Ernesto ScofTone Plate 41. John C. Sheehan

Plate 42. M.M. Shemyakin Plate 43. Tetsuo Shiba

260 Appendix

Plate 44. R.L.M. Synge

Plate 46. Wang Yu

Plate 45. Emil Taschner (1900-1982)

Plate 47. Friedrich Wessely von Kamegg (1897-1967) (Courtesy Prof. K. Schliigl)

Appendix 261

Plate 48. Friedrich Weygand (1911-1969) Plate 49. Bernhard Witkop

Plate 50. Robert B. Wordward Plate 51. Erich Wunsch

262 Appendix

Plate 52. Haruaki Yajima Plae 53. Geoffrey T. Young

Plate 54. The insulin group of Helmut Zahn (Photo M. Forschelen, Aachen) from left: H. Bremer, O. Brinkhoff, H. Zahn, R. Zabel, E. Schnabel, J. Meienhofer

Plate 55. Leonidas Zervas (1902-1980) at the age of about 60

Appendix 263

264 Appendix

Abderhalden. Emil, 1877-1950 (p. 34, Plate 8) born in Oberuzwil, Switzerland, studied medicine in Basel where he graduated as M.D. in 1902. In the same year he moved to Berlin to join Emil Fischer, where he combined chemistry with enzymology (p. 35). In 1908, he was appointed Professor of Physiological Chemistry at the School of Veterinary Medicine in Berlin. In 1911 he became Professor and Head of the Institute of Physiology of the University of Halle/Saale where he worked on the physiology and biochemistry of pep tides, proteins and enzymes. Abderhalden was President of the "Deutsche Akademie der Naturforscher Leopoldina" from 1931 until 1945, the year in which he and his family were moved to West Germany by American troops. He died in 1950 in Ziirich, Switzerland.

Akabori, Shiro (p. 116, Plate 9) born in Shizuoka Prefecture, Japan, in 1900, graduated from Tohoku Imperial University in 1925, research associate in the laboratory of Prof. Toshiyuki Majima and received his Doctor of Science degree from the same university in 1931. He studied in the laboratory of Prof. E. Waldschmidt-Leitz in the German University at Prague, Czechoslovakia from 1932 to 1934, appointed as Assistant Professor at Osaka Imperial University in 1935 where he advanced to full Professor (1939), Dean of the Faculty of Science (1947), and the President (1969). He established the Insitute for Protein Research at Osaka University and served as the first Director of the Insitute (1957). Since retiring from Osaka University (1965), he has been the President and a trustee of the Protein Research Foundation to which the Peptide Institute belongs. He is a member of the Japanese Academy, and a member of numerous foreign Academies.

Bayer. Ernst (pp. 54, 234, Plate 10) born in 1927 in Ludwigshafen/Rhine, studied chemistry in Heidelberg, FreiburgfBr. Dr. rer. nat. 1954, from 1958 at the Technical University, Karlsruhe and University of Tiibingen, there associate professor in 1962, full professor in 1965.

Bergmann. Max, 1886-1944 (p. 45, Plate 3) born in 1886 in Fiirth, Bavaria, begun studies of botany at the Technical Highschool in Munich, transferred to chemistry in E. Fischers laboratory in Berlin, where he worked on his doctoral thesis, 1911. Fischer engaged him as assistant in his personal laboratory to work in the field of, among other topics, amino acids and peptides. In 1920 he was appointed Acting Director at the Kaiser-Wilhelm-Institute for Fiber Research in Berlin-Dahlem. In 1922 he moved to Dresden as Director of the Kaiser-Wilhelm-Institute for Leather Research, where he, with Leonidas Zervas, invented the benzyloxycarbonyl group for the reversible protection of amino groups (p. 46). In 1934, Bergmann had to leave Nazi Germany. He was kindly received by the Rockefeller Institute for Medical Research in New York City, where he successfully continued his investigations of amino acids and peptides with excellent collaborators (S. Moore, E. Stein et al.) (see p. 50) Bergmann died in 1944,58 years old, after a long illness in New York.

Biemann. Klaus (p. 128) born in Innsbruck, Austria in 1926. He studied chemistry at his home Univ., and received his PhD in 1951. He was instructor of chemistry there until 1955 when he became Professor of Chemistry at the Massachusetts Institute of Technology, Cambridge USA and has applied mass spectrometIY. in his investigations since then.

Blaha. Karel, 1926-1987 (pp. 122,231, Plate ll)was born in 1926 near Pilsen, Bohemia. In 1949, after graduating in chemistry at the Technical University in Prague, he joined -the Laboratory of Heterocyclic compounds led by Rudolf Lukes where he worked and gained experience of organic chemistry in depth. In 1960, Blaha went to the Institute of Organic Chemistry and Biochemistry of the Czechoslovak Academy of Sciences, and started his successful research in peptide chemistry, at first as a coworker of Joseph Rudinger, and after Rudinger's emigration (1968) his successor as Head of the Department.

Bodanszky, Miklos born in 1915 in Budapest, Hungary, received his doctorate at the Technical University of Budapest. After a few years in the pharmaceutical industry he was appointed as Head of the natural products department of the Institute for Medical Research and at the time became a lecturer in Medicinal Chemistry at the Technical University of Budapest. His work on active esters

Appendix 265

started in this period (p.85). In 1956, he left Hungary and joined V. du Vigneaud, at Cornell University Medical School in New York City. Here he demonstrated the stepwise strategy in a novel synthesis of oxytocin. In 1959 he joined the Squibb Institute for Medical Research, where with his coworkers (among them Miguel A. Ondetti) he reported the first synthesis of the gastrointestinal hormone secretin (p. 167). From 1966 until his retirement in 1983 he was professor of Chemistry and Biochemistry at Case Western Reserve University in Cleveland, Ohio.

Brenner, Max (pp. 58, 197,242, Plate 12) born in 1915 in Chur, Switzerland. Studied chemistry at the Technical University, Zurich, Diploma Chemical Ing. in 1937, Dr. Sc. techno after thesis with L. Ruzicka. Thereafter one year working at Rockefeller Institute in New York with Max Bergmann on synthetic substrates for proteases, 1941-1947 research in the pharmaceutical-chemical industry, 1947 assistant to T. Reichstein, 1949 Lecturer, 1954 Professor until 1980 at the University of Basel.

Brockmann, Hans, 1902-1988 (p. 118, Plate 13) born in 1903 in Altkloster near Hamburg, received his Dr. degree at the Univ. of HallejSaale (with E. Abderhalden, in 1930, went to Richard Kuhn at the Kaiser-Wilhelm (later Max-Planck)-Institute for Medical Research in Heidelberg where he did pioneering work on chromatography, e.g. of carotenoids. In 1935 he became Head of the biochemical department of the Chemistry Institute of the Univ. of Gottingen (Director Adolf Windaus), in 1941 Prof. at the Univ. Posen, and after the war, in 1945, successor of A. Windaus in Gottingen until retirement in 1972. Antibiotica (actinomycin, p. 224 etc) ionophores (valinomycin, p. 201).

Bruckner, Viktor, 1900-1980 (pp. 41,236, Plate 14). Born in 1900 in Kesmark a small Carpathian town, graduated from the Technical University in Budapest, thereafter studied with Alexander Schonberg (Berlin) and Fritz Pregl (Graz), then with Albert von Szent-Gyorgyi in Szeged (Hungary). Engaged in peptide chemistry from 1937 (bacterial capsular substances), in 1950 appointed as Director of the Institute of Organic Chemistry of the Eotvos Lorand University in Budapest. Died in Budapest in 1980.

Craig, Lyman C, 1906-1974(p. 55, Plate 16) son ofa farmer, was born in Palmyra, Iowa. In 1932, with a fresh Ph.D. degree from the University ofIowa at Ames, he moved to Baltimore to work at the Johns Hopkins University as a National Research Council fellow. Two years later Craig joined the Rockefeller Institute in New York City to collaborate with A. Jacobs on the structure-elucidation of ergot alkaloids. Here he developed the fractionation of mixtures by repeated extraction procedures. Countercurrent distribution (CCD) turned out to be of great value in the isolation of natural and synthetic products. The definitive determination of the molecular weight of insulin, for instance, became possible through the isolation of the least substituted derivative by CCD. For the concentration of solutions recovered from CCD, he invented the rotary evaporator.

Lyman C. Craig remained at the Rockefeller Institute during his entire career and was appointed Professor when the Institute became a University. His work was recognized by numerous awards. He died in 1974.

Curtius, Theodor, 1857-1928 (p. 25, Plate 2) born in Duisburg (Rhineland). He first studied music and natural sciences in Leipzig until 1876, and went after his military service in 1878 to Heidelberg to study chemistry with Robert Bunsen. He returned to Leipzig where he received his Ph.D. degree after a thesis guided by Hermann Kolbe in 1882 (first synthesis of a peptide, p. 26), moved to the University of Munich (A. Baeyer), where he was assistant from 1884-1886. In 1886 he graduated Dr. habil. at the University of Erlangen, in 1889 he moved as full professor to the University of Kiel. A call in 1892 to the University of Wurzburg as successor to Emil Fischer was not accepted, but he succeeded A.V. Kekule in Bonn in 1897, although for only one year until 1898 when he succeeded Victor Meyer at the University of Heidelberg as Head of the Chemical Institute. There he worked until the end of his life in 1928.

du Vigneaud, Vincent. See biography on pp. 153-155.

266 Appendix

Edman. Pehr Victor, 1916-1977 (pp. 118,240, Plate 15) born in Stockholm in 1916, matriculation examination in 1935, studied medicine at the Karolinska Institute Medical School in Stockholm from 1935, Bachelor of Medicine in 1938, graduation as a physician in 1946. Concurrently with his studies in medicine he started his training in biochemistry with Erik Jorpes. for a short time also with Hugo Theorell, and soon started a project on angiotensin that led to a MD thesis. Then he widened his experience in protein chemistry during one year at the Rockefeller Institute in Princeton with Northrop and Kunitz (crystallization of proteolytic enzymes). On his return to Sweden, Edman was awarded an associate professorship in Lund in 1947 where he conducted his stepwise peptide degradation work (p. 118) between 1950 and 1956. In 1957 Pehr Edman accepted an otTer to be Director of Research at St. Vincent's School of Medical Research in Melbourne, Australia, where he remained for 15 years, during which the work on an automated sequence analyzer was finished in 1967. From 1972 until his death from a brain tumor in 1977 he was Director of the Department of Protein Chemistry of the Max-Planck-Institute for Biochemistry in Martinsried near Munich.

Erspamer. Vittorio (pp. 134,238, Plate 17), born in Malosco (Trento, Italy) in 1909, studied Medicine at the University of Padua (M.D. in 1939), was there assistant at the Institute of Comparative Anatomy and Physiology from 1935-1938, then postdoctoral fellow at the Universities of Berlin and Bonn, at the Institute of Pharmacology University of Ro~e, 1940-1947, Professor of Pharmacology University of Bari Medical School until 1955, University of Parma Medical School until 1967 and from then to 1984 Director of the Institute of Pharmacology, University of Rome. Ersparmer's work comprised comparative pharmacology and biochemistry of biogenic amines (17 new compounds) and, particularly, bioactive peptides (40 compounds) from invertebrates and lower vertebrates (amphibian skin) (see p. 184). The opioid peptides (demorphis and deltorphins) are the most potent among all natural peptides.

Fischer. Emil, 1852-1919 (p.24, Plate I), son of a merchant was born in 1852 in Euskirchen (Rhineland) studied chemistry in Bonn (KekuU~), StraBburg (A. Baeyer, physics; A. Kundt) where he graduated Dr. phil. in 1874. Assistant with Baeyer, from 1874 in Munich. Professor in Erlangen (1882-1885), then in Wiirzburg until his call to the famous Chemical Institute of the University of Berlin as successor to A.W.v. Hofmann, in 1892. Amino acid and peptide research from 1900, after extremely successful research in the field of carbohydrates and purines. Fisher died in the summer of 1919 in Berlin. He was the second winner of the Nobel Prize for Chemistry in 1902, after van t'HotTin 1901.

Fruton. Joseph S. (pp. 56,246, Plate 18), born in 1911 in Czestochowa, Poland Ph.D. at Columbia University, New York, in 1934, at the Rockefeller Institute with Max Bergmann 1934-1935 (p. 47). In 1945 he became Associate Professor of Physiological Chemistry at Yale University, New Haven, Conn., Chair of the Department of Biochemistry 1951-1967, Eugene Higgins Professor of Biochemistry 1957-1982, Professor of the History of Medicine 1980-1982. Published, among others, General Biochemistry (with S. Simmons, 1953), Molecules and Life (1972), and selected articles on the History of Biochemistry and Chemistry since 1800.

Geiger. Rolf, 1923-1988 (pp.93, 234, Plate 19), born in Bodman on Lake Constance, studied chemistry at the University of Tiibingen (1949) and completed his training in 1956, at the Technical University in Berlin, with a doctoral thesis under Friedrich Weygand. In the following year he initiated peptide chemistry in the Pharma Synthese Laboratories at Hoechst A.G. In 1969, Geiger became the leader of the peptide group. First a part time lecturer at the University of Frankfurt a.M., in 1979 he was named Honorary Professor. With his group he worked successfully on the synthesis of hormones, such as adrenocorticotropin or insulin, and of releasing factors. Among his many excellent coworkers Wolfgang Konig (Plate 20) also a student of F. Weygand, is mentioned here because of his large share in the development of racemization-free coupling methods.

Goodman. Murray (p. 246) born in New York N.Y. in 1928, studied chemistry at Brooklyn College and the Univ. of California and received his Ph.D. in 1952. He was a Research associate at MIT 1952-55, was Prof. of Chemistry at Poly tech Institute Brooklyn 1956-71 and is now Prof. of Chemistry, Univ. of California, San Diego.

Appendix 267

Gross, Erhard, 1928-1981 (p, 62) was born in 1928 in Wenings near Frankfurt a, M" studied chemi­stry at the Universities of Mainz and Frankfurt. After his Dr. Degree with Th. Wieland he went to Bernhard Witkop at the National Institute of Arthritis and Metabolic Diseases, NIH in Bethesda, Maryland, USA. In 1968 Gross was appointed Chief of the Section on Molecular Structure, Laboratory of Biomedical Sciences, and in 1973 Section Reproduction Research Branch at the National Institute of Child Health and Human Development, NIH. He died tragically in a road accident in 1981. His name is connected with the cyanogen bromide cleavage of pep tides (p. 117), the structure of nisin (p. 222), channel forming peptides, and outstanding literary contributions to the peptide and protein field.

Guillemin, Roger (p. 246) born in Dijon, France, in 1924 studying medicine at the Univ. of Dijon, received his M.D. in 1949 and his Ph.D. at the Univ. of Montreal in 1952. There he became assistant professor and assistant director of the Institute for Experim. Medicine and Surgery (1951-53), then at Baylor College of Medicine, Houston Tex. until 1963. He is now Chairman of the Laboratories of Neuroendocrinology, Salk Institute, La Jolla, Cal. He was awarded the Nobel Prize for Medicine and Physiology (shared with A. Schally) in 1977.

Hirschmann, Ralph Franz (pp. 41,247) born in 1922 in Bavaria, Ph.D. in organic chemistry in 1950 at the University of Wisconsin. Started professional experience in Research Laboratories at Merck Sharp u. Dohme in 1950 and advanced to become director of peptide research, 1968, then of protein research, director medicinal chemistry of the company in West Point, Pa. 1974-76 Vice President of basic research in the Company at Rahway, N.J.

Hodgkin, Crowfoot Dorothy (p. 132, Plate 21) born in 1910 in Cairo, she studied chemistry at Oxford from 1928-32 and concentrated on X-ray crystallography with J.D. Bernal at Cambridge; in 1934 she returned to Oxford where she has remained, except for brief intervals, ever since. She became University lecturer and demonstrator in 1946, University Reader in X-ray crystallography in 1956 and Wolfson Research Professor of the Royal Society in 1960-1983. Apart from X-ray studies of insulin (p. 159) she also did research on penicillin (in 1942) and on vitamin B12 (in 1948). She received the Nobel Prize in chemistry 1964. In 1937 she married Thomas Hodgkin, historian of Africa and the Arab world.

Hofmann, Klaus Heinrich (pp. 38,41,163) born in Karlsruhe, Germany, in 1911, studied chemistry at the Swiss Federal Institute of Technology (ETH, Ziirich), was awarded his Ph.D. in 1936. He became fellow of the Rockefeller Foundation 1938-40; assistant at the Medical College, Cornell Univ. 1940-42; assistant and then associate prof. 1944-47. He has been research prof. of biochemistry and Prof. of the Biochemistry School of Medicine, Univ. of Pittsburgh, Director of Protein Research Laboratories since 1964.

Hofmeister, Franz, 1850-1922 (p. 2, Plate 22) born in Prague, son of a physician, studied medicine at the ancient University, worked on "peptones" (Habilitation). Thereafter, six months with the pharmacologist O. Schmiedeberg in StraBburg (then German Alsace), from 1885-1896 director of the Institute of Pharmacology in Prague. In 1896 professor of Physiological Chemistry, successor of Felix Hoppe-Seyler in StraBburg. After the return of Strasbourg to French rule (1919) he left and found a haven in Wiirzburg, where he was named Honorary Professor and worked on vitamins until shortly before his death in 1922.

Hruby, Victor J. (p. 246), born in Valley City, N. Dakota USA in 1938, Ph.D. Cornell Univ. 1965, Prof. of Chern. Univ. of Arizona since 1977. He became interested in peptide hormones as a postdoctoral fellow with Nobel prize-winner Vincent du Vigneaud at Cornell University in the late 1960s just before he joined the University of Arizona faculty. In the 20 years since, he has become a world leader in this important research field (synthesis, isolation, conformations, dynamics, mechanisms of action, and structure-activity relationships of peptide hormones and neurotransmitters and their analogs). He is the editor of the International Journal of Peptide and Protein Research as successor to Choh Hao Li who died in 1988.

268 Appendix

Jorpes, Erik J., 1894-1973 (pp. 166,241, Plate 23) was born on the Finish island Kokar in the Aland archipelago, when Finnland was part of the Russian Empire. He worked together with V. Mutt with great success on the chemistry and physiology of the gastro-intestinal hormones at the Karolinska Institute in Stockholm, Sweden, where he died in 1973.

Karle, Isabella L. (p. 133) born in Detroit, Mich., in 1921, studied chemistry at the Univ. of Michigan, Ph.D. 1944. Associate chemist at Univ. Chicago, instructor there and physicist 1946-59, now Head of X-ray analyt. section of U.S. Naval Res. Lab. Washington D.C. Married to Jerome Karle (born in 1918 in New York City, Nobel Prize for Chemistry 1987)

Katchalski, Ephraim (Katzir) (pp. 40, 237, Plate 24) born 1916 in Kiev (Ukraine); Hebrew University Jerusalem, 1951-73; Professor and Head of the Dept. Biophys. Weizmann Institute of Sciences, Rehovot; President of Israel 1973-78; 1978 Professor at Tel-Aviv University. Syntheses and properties of polyamino acids are linked with his name.

Katsoyannis, Panayotis (p. 160, Plate 26) born in Greece in 1924, studied chemistry at the National Univ. Athens with L. Zervas; Ph.D. in 1952. Research associate at the Medical College of Cornell Univ. Ithaka N.Y. (1952-56), associate prof. School of Medicine, Univ. of Pittsburgh (1958-64), at Medical Res. Center Natl. Lab. Brookhaven unti11968 now Professor of Biochem. and Chairman Mount Sinai School of Medicine, New York City. The synthesis of insulin was his field.

Kenner, George Wallace (pp.24, 81, Plate 27). Born 1922. Graduated in Chemistry, University of Manchester, 1939. His early research was with A.R. Todd at Manchester and then at Cambridge, on purine and pyrimidine chemistry and the synthesis of nucleosides. In 1957 appointed Head of the Department of Organic Chemistry, University of Liverpool. Elected Fellow of the Royal Society in 1964. Just before his death in 1978 he was appointed a Royal Society Research Professor, holding his appointment at Liverpool.

Lederer, Edgar, 1908-1988 (pp. 129, 232, Plate 28). Born in 1908 in Vienna, Austria, studied Chemistry at University of Vienna (Dr. phil., 1929); postdoctoral research at Kaiser-Wilhelm-Institut Heidelberg, 1930-1933, with Richard Kuhn, where he revived in 1931, Mikhail Tswett's chroma­tography with carotenoide mixtures. He was from 1933-35 Research fellow at the Inst. de Biologie Physico-Chimique, Paris, director of Dept. of Organic Synthesis, Vitamin Inst. Leningrad 1936-37. After Army service, he carried out research at Laboratoire de Biochimie, Lyon, from 1940 to 1947, then Maitre des recherches with Inst. de Biologie Physico-chimique until 1960. Director Dept. de Chimie Biologique, Inst. de Chimie des Substances Naturelles CNRS 1960-1978. Died in 1988 in Paris. Lipopeptides, immuno adjuvants, mass spectrometry were among his studies.

Leuchs, Hermann (1879-1945, p.35, Plate 29) born in 1879 in Nuremberg, studied chemistry in Munich and graduated in 1902, Ph.D. with a thesis guided by E. Fischer in Berlin. He then became associate professor there and, in 1926 Associate Director of the Institute of Chemistry of the University. After his discovery of the "Leuchs' substances" (p. 35) in 1906 and some of their reactions he turned to strychnine chemistry on which he worked until his death in the destroyed Berlin in 1945.

Li, Choh Hao, 1913-1987 (p. 246, Plate 30) was born in Canton, China, in 1913 and had his early schooling there, graduating from Pui Ying High School in Canton in 1929, and receiving his B.Sc. in Chemistry from the University of Nanking in 1933. In 1938 he was granted provisional admission to the University of California, Berkeley, and went on there to his doctorate in physical-organic chemistry. It was in the laboratory of Herbert Evans at Berkeley that Li began to develop the techniques that would eventually lead to the isolation and structure determination of several peptide and protein hormones found in the brain including growth hormone and beta-endorphin. From 1950 he headed the Hormone Research Laboratory as Professor of Biochemistry and of Experimental Endocrinology first at Berkely then at San Francisco. After his retirement in 1983 he continued his research and his numerous editorial activities until his death in 1987.

Appendix 269

Lipmann, Fritz, 1899-1988 (p. 208) born in Konigsberg, East Prussia in 1899, he became Dr. med. at the Univ. of Berlin in 1924. Assistant at Kaiser-Wilhelm-Institutes for Biology in Berlin and Medical Research in Heidelberg 1927-31, Carlsberg Institute Copenhagen 1932-39, research associate Medical College of Cornell Univ. 1939-41, Head of Biochem. Res. Lab. and Prof. at Harvard Univ. and Mass. General Hospital 1941-47, then Professor at Rockefeller Univ., New York. Nobel Prizefor Medicine and Physiology 1953. Coenzyme A, peptide biosynthesis.

Martin, Archer John Porter (pp. 52, 54, Plate 31) born in 1910 in London, studied chemistry in Cambridge (Ph.D.) worked there in the physical chemical laboratory on nutritional research, then in the Wool Institute Leeds until 1946. Member of staff of the Medical Research Council, director Natl. Inst. Medical Res., Mill Hill (until 1956), later various professorships, e.g. Ecole poly technique, Lausanne 1980-1983. Nobel Prize in chemistry 1952, shared with R.L.M. Synge with whom he worked in Leeds on chromatographic methods.

Merrifield, Bruce R. (p. 103, Plate 5) was born in Fort Worth, Texas, in 1921. His parents moved to California when he was two years old and it was in California where he received all his education and also his training in chemistry. After two years in Pasadena Junior College he transferred to the University of California in Los Angeles (UCLA). Following graduation he worked for a year at the P.R. Park Research Foundation but returned to UCLA for graduate training in biochemistry. His studies, guided by Professor M.S. Dunn, were concluded with the Ph.D. degree, that was awarded on June 19, 1949. The next day he married Elizabeth Furlong Oater his coworker) and the day after they moved to New York City to joint Dr. D.W. Woolley at the Rockefeller Institute. Since 1959 he has dedicated his research to the solid phase idea and developed his famous method of peptide synthesis.

Merrifield advanced in rank at the Rockefeller University to Professor and received numerous awards and honorary degrees elsewhere. In 1984 he was named John D. Rockefeller professor and in the same year received the Nobel Prize in Chemistry.

Moore, Stariford, 1913-1982 (p. 50, Plate 4). Born in Chicago, Illinois, in 1913. On graduation from Vanderbilt University in Nashville, Tennessee, with summa cum laude and as a Founder's Medalist, he entered the University of Wisconsin for graduate studies. There he studied organic chemistry under Homer Adkins and worked on his Ph.D. thesis in biochemistry under the guidance of Karl Paul Link, a friend of Max Bergmann whom he joined at the Rockefellerinstitute in 1939. The work involved the determination of amino acids by precipitation with selective reagents used at two different concentrations ("solubility product method") in collaboration with W.H. Stein. During the war Dr. Moore served from 1942 to 1945 in the Office of Scientific Research in Washington, D.C. On returning to the Rockefeller Institute, after Bergmann's death in 1944, Moore continued the effort in collaboration with William Stein applying chromatography and the important "amino acid analyzer" (p. 51). The new method was applied by Moore, Stein and Hirs, in the same laboratory for the elucidation of the primary structure of ribonuclease A with 124 amino acid residues. Stanford Moore, in recognition for these invaluable achievements, shared the Nobel Prize in Chemistry in 1972 with W.H. Stein. He held a chair as a visiting professor at the University of Bruxelles, Belgium, and received an honorary doctorate from the same university and was a chair-professor at Rockefeller University. The names of Stanford Moore and William H. Stein are linked together forever. Yet, fate added still another link to their association, a tragic one. In 1982, threatened by paralysis, similar to that of Stein's, Professor Moore took his own life.

Mutt, Viktor (pp. 167,241, Plate 23) was born in 1923 in Tartu, Estonia, moved to Sweden in 1944 after one year in Finnland, worked with E.J. Jorpes with great success on the chemistry and physiology of gastrointestinal peptides at the Karolinska Institute in Stockholm, Sweden.

Ondetti, Miguel Angel (Plate 32) born in 1930 in Buenos Aires, Argentina, completed his studies in chemistry at the University of Buenos Aires in 1957 with a Doctor of Natural Sciences degree received for his work on alkaloid chemistry under V. Deulefeu. Soon after, he joined the Squibb Institute for Medical Research and continued his research at the Institute, also after his transfer to the United States in 1960. There, for several years, he participated in an effort, led by M. Bodanszky, toward the synthesis of peptide hormones, including the first synthesis of secretin and became

270 Appendix

coauthor of one of the earliest monographs on peptide synthesis. Subsequently Ondetti initiated and led a major endeavor in the area of anti-hypertensive agents that resulted in the discovery of ACE inhibitors (p. 183), a new class of compounds that has gained considerable importance in the treatment of hypertension and other cardiovascular disorders.

Ovchinnikov. Yuri A., 1934-1988 (p.202, Plate 33) born in Moscow, studied chemistry at the Lomonosov Moscow State University and entered in 1960 the laboratory ofM.M. Shemyakin in the Institute of Chemistry of Natural Products (later "Shemyakin Institute of Bioorganic Chemistry") of the USSR Academy of Sciences in Moscow. Research on depsipeptides, in 1964 in Ziirich with V. Prelog stereochemistry of cyclic peptides; back to Moscow-membrane active peptides, proteins. After Shemyakin's death in 1970 he became Academician, Head of the institute, and at the age of 40, Vice President of the Academy. He died in 1988 after a two- years struggle with advancing disease.

Patchornik. Abraham (p. 237, Plate 25) born in 1926 in Nes-Ziona, Israel, studied chemistry at the Hebrew University Jerusalem, where he obtained his Ph.D. with Prof. E. Katchalski. In this time he was research assistant at the Weizmann Institute in Rehovot. There he became Professor at the Department of Biophysics in 1968, and Head Department of Organic Chemistry in 1972. His carrier in Israel was supplemented by a Fellowship with B. Witkop in Bethesda, Md. (1957/58) and Research visits with N.O. Kaplan (Brandeis, 1961) and R.B. Woodward at Harvard, 1965/66. Patchomik developed the field of non-enzymatic degradation of peptides and proteins, e.g. by bromination at the indole and imidazol nucleus, studied photosensitive blocking groups and polymeric reagents.

Pauling. Linus (p. 257, Plate 34) born in 1901, educated at Oregon State College, Calif. Inst. of Techno!. (Caltec) and Universities of Munich, Copenhagen and Ziirich. After being assistant at Oregon State Coli. and Caltec, he was there Asst. Prof. 1927-29, Assoc. Prof. 1929-31, Prof. 1931-64; Prof. of Chemistry Univ. of Calif., San Diego 1967-69, Stanford Univ.1969-74, since then Prof. emer. Member of numerous Academies, among a multitude of degrees and prizes he won the Nobel Prize for Chemistry in 1954, for Peace in 1962. Among numerous fundamental contributions to general chemistry he suggested secondary structure of peptide chains (with R.B. Corey IX-helix, pleated sheets, p. 13), Vitamin C and longevity.

Photaki. Jphigenia, 1921-1983 (p. 257, Plate 35) born in Corinth, Greece, studied chemistry at the University of Athens. Her research, guided by Leonidas Zervas, led, in 1950, to the degree of Doctor of Natural Sciences. After postdoctoral studies in Switzerland, with Max Brenner and H. Erlenmeyer, and later also with V. du Vigneaud in New York, she rejoined the Department of Chemistry at the University of Athens, advanced in rank and, in 1977, was promoted to full Professor. Her outstanding work, particularly her studies of cysteine- and serine-containing peptides, gained worldwide recognition, but was sadly terminated by her untimely death in 1983.

Rothe. Manfred (pp. 40, 196) born in 1927 in Halle/Saale studied chemistry in Rostock. Habilitation in Halle, transferred to the Univ. of Mainz in 1961 where he became associate Professor in 1966, since 1974 full Professor at Univ. of Ulm (peptides of proline, cyclols).

Rudinger. Joseph. See biography on pp. 155-157.

Rydon. Norman (p. 243, Plate 36) born in 1912 studied chemistry at London (B.Sc. 1931, Ph.D. 1933, D.Sc. 1938), D. Phil., Oxford 1939. Chemical Defence Experimental Section, 1940-1945. From 1945-1947 Member of Scientific Staff of the Lister Institute, then Reader at Birkbeck College, London, until 1949 and from 1949-1952 Reader at Imperial College, London. Professor at Manchester College of Science and Technology 1952-1957, Professor and Head of Department, Exeter University 1957-1977. Rydon's work outside of peptide research was on natural substances; peptide topics at Exeter included cysteine peptides, sequential polypeptides, synthetic studies of ferredoxins. Chlorination followed by starchh-potassium iodide for the detection of peptides is known as Rydon-Smith reagent.

Appendix 271

Sakakibara, Shumpei (p. 67, Plate 37) born in Kobe, Japan in 1926, graduated from Osaka University in 1951, research associate in the laboratory of Professor Shiro Akabori at Osaka University and received his doctor of science degree from the same University. From 1960 to 1962, he studied in the laboratory of Professor George Hess in Cornell University, Ithaca, where he had an opportunity of handling liquid HF as a solvent of pep tides and proteins. After returning from the Cornell University, he was appointed Head ofthe Peptide Center, Institute for Protein Research, Osaka University as an Associate Professor, he demonstrated usefulness ofHF as a deprotecting reagent. In 1971, he resigned from Osaka University, organized the Peptide Institute in the Protein Research Foundation serving as the research director. In 1977, he organized the Peptide Institute, Inc. outside of the Foundation, served as the president, headed a research group for peptide synthesis and made a success of the Foundation's business of distributing biologically active peptides.

Sanger, Frederick (Plate 38) born in 1918 in Rendcombe (Gloucestershire), studied at St. John's College, Cambridge. Biochemical research at Cambridge from 1940, Ph.D. in 1943, 1951-1983 Member of the Scientific Staff of the Medical Research Council, Nobel prizes in Chemistry 1958 and 1980 for sequencing polypeptides (insulin) and nucleic acids, resp. "Sangers reagent", 2,4-dinitrofluorobenzene (p. 115).

Schally, Andrew V. (p. 172) born in Wilno, Poland in 1926, studied biochemistry at McGill Univ. Montreal. Ph.D. 1957. Assistant at Nat!. Institute for Medical Res. England (1949-52), associate endocrinologist at Allan Memorial Institute of Psychiatry, Canada (1952-57), assist. prof. protein chemistry and endocrinology at Baylor College of Medicine, Houston, Tex. until 1962, associate prof. unti11966. Prof. School of Medicine, Tulane Univ. New Orleans, Chief Endocrinol. and polypeptide Laboratories at Veterans Administration Hospital. Nobel Prize for Medicine and Physiology 1977 (shared with R. Guillemin).

Schwyzer, Robert (pp. 84,205, Plate 39) was born in Zurich, Switzerland, in 1920, but he received his primary and secondary education in the United States. The family later returned to Switzerland and he studied chemistry in Zurich, completing his experimental work for his Ph.D. degree under Paul Karrer. After some years in industry (CIBA), he accepted an invitation to join the faculty of the Federal Institute of Technology (ETH) in Zurich, as professor. Schwyzer first synthesized angiotensin (p. 205), gramicidin S (where he detected cyclodimerization) and, last but not least, the 39-residue sequence of ACTH. He proposed cyanomethyl esters for the formation of the peptide bond.

Schwyzer introduced the concepts of "homodetic" and "heterodetic" cyclopeptides. Similar conceptualization of architectural aspects of biologically active peptides and of the relation of sequence and geometry to biological activity was expressed in the nomenclature proposed by him with terms such as "address sequences", "sychnologic organization" (continuate words) and "rhegnylogic organization" (discontinuate words). These thoughts and suggestions, for instance his more recent membrane-compartment model, were not merely intellectually stimulating but also pointed out new directions in hormone research.

Scoffone, Ernesto, 1923-1973 (p. 237, Plate 40) born in 1923 in Udine, Italy, studied pharmacy at Univ. of Bologna (Ph.D. 1946) and chemistry at Univ. of Padua (Ph.D. 1950). Postdoctoral work at Rockefeller Univ. New York City in 1959/60. From 1960 associate Prof. Univ. Padua, in 1965, full Prof. of organic chemistry at the same Univ., and director of the Centre for Macromol. Chemistry of C.N.R.

ScotT one established synthetic peptide chemistry in Italy by work of his group on S-peptide of ribonuclease A, new protecting groups and methods of modification and fragmentation of proteins.

Sheehan, John C. (pp.88, 199, Plate 41) born in Battlecreek, Michigan, 1915, received his Ph.D. degree at the University of Michigan in 1941. After a few years in the pharmaceutical industry (Merck) he joined the faculty of the Massachusetts Institute of Technology where he advanced to full Professor and where he remains actively engaged in research even after his retirement in 1976. He also served as Scientific Liaison Officer of Naval Research and as Editor in Chief of the Journal of Organic

272 Appendix

Chemistry. For his important contribution to the synthesis of penicillins, amino acids, peptides, alkaloids and explosives Sheehan has received numerous awards.

Shemyakin, Michail M., 1908-1970 (pp. 20,202, Plate 42). Laid the basis of bioorganic chemistry in the USSR. Academician (1958). Graduated from Moscow State University (1930). Founder and first Director of the Institute for Natural Products, USSR Academy of Sciences. (In 1974 the Institute was given the name "The Shemyakin Institute of Bioorganic Chemistry"). Chemistry of naturally occurring biologically active compounds. With A. Braunstein he developed a general theory of pyridoxal enzyme action. Synthesis of antibiotics, vitamins, amino acids, quinones, total tetracycline synthesis (1966). He published many papers on the structure and function of proteins, peptides, and biologically membranes.

Shiba, Tetsuo (p.222, Plate 43) born in Hiroshima Prefecture, Japan in 1924, received his Ph.D. degree at Osaka University in 1959. After having studied at the National Institute of Health, Bethesda, USA, as Visiting Scientist for two and a half years, he returned to Osaka University as Associate Professor in 1962. In 1971 he was appointed Professor, Laboratory of Natural Product Chemistry, Department of Chemistry, Faculty of Science, Osaka University. Here he developed his structural and synthetic studies on biologically active substances (peptides and others). In the meantime, he served as Vice President of the Chemical Society of Japan, and now as a Member of the Science Council of Japan. He successfully planned the Japan Symposia of Peptide Chemistry and the first international Symposium of Peptide Chemistry in Japan as President of the Organizing Committee in 1987.

He retired from Osaka University in 1988, however, he is still continuing his scientific activity as the Director of the Peptide Institute, Protein Research Foundation, Japan, which was founded by S. Akabori.

Stein, William H. 1911-1980 (p. 50, Plate 4) was born in New York City, in 1911. He graduated from Harvard University in 1933 with a B.Sc degree, after one year he transferred to Columbia University. Research guided by Hans Clark, on the protein elastin had a lasting influence on the direction of his scientific interests. Another Columbia professor, Erwin Brand, introduced him to the recently arrived Max Bergmann. Thus, after graduation from Columbia with a Ph.D. degree in 1937 he joined Bergmann at the Rockefeller Institute where he remained throughout his career. At Rockefeller the young researcher was surrounded by other young scientists of real excellence, to name a few: Stanford Moore, Joseph S. Fruton, Emil Smith, Klaus Hofmann, Paul Zamecnik. W.H. Stein participated in an effort aiming at the quantitative determination of the amino acid composition of proteins by the "solubility product" method of Bergmann (p. 48). In the years following Bergmann's death in 1944, Stein and Stanford Moore applied chromatographic procedures for the separation of amino acids in the hydrolysates of proteins, at first partition chromatography, later by application of ion-exchange chromatography (p. 50). A fully automated instrument, the "amino acid analyzer" was developed in collaboration with D.H. Spackman in 1958. Stein and Moore together with C.H.W. Hirs, addressed themselves to the elucidation of the structure of the enzyme ribonuclease A, and they solved the entire covalent structure of the chain of 124 amino acid residues (p. 51). Dr. Stein's work received wide recognition. When the Rockefeller Institute was reorganized to Rockefeller University he was appointed Professor. In 1972 he received the Nobel Prize in Chemistry (shared with Stanford Moore). In 1980 he died, paralyzed by a rare disease, in New York.

Synge. Richard Laurence Millington (p.52, Plate 44). Born in 1914 in Liverpool, he studied Biochemistry at Cambridge, Int. Wool Seer. 1938, Biochemist at Wool Industries Research Association, Leeds 1941-1943, Staff Biochemist Lister Inst. of Preventive Medicine, London, until 1948, then Head of Dept. of Protein Chemistry, Riwett Research Inst. Bucksburn, Aberdeen (1948-67), Biochemist, Food Research Institute, Norwich, 1967-1976. Shared Nobel Prize for Chemistry with AJ.P. Martin, 1952 for invention of partition chromatography.

Taschner, Emil, 1900-1982 (p.239, Plate 5) was born in Cracow, studied chemistry there at the Jagiellonian University in 1920, later in Vienna where he received his Ph.D. degree in 1927. After

Appendix 273

postgraduate studies in Paris (Pasteur Institute, University) he returned to Cracow to work in the Pharmacological Department and in pharmaceutical industries. The years of World War II he spent in Lwow as a workman in hiding. After the War he moved to the Chemistry Department of the University in Wroclaw, in 1953 he was appointed Head of the Department of General Chemistry at the Technical University of Gdansk, later of Peptide Chemistry Department until his retirement in 1971. Taschner was the founder of peptide chemistry in Poland in the early fifties with studies of protection, deprotection and racemization of amino acids.

Ugi. Ivar (pp. 99,233) born in 1930 in Estonia studied chemistry at the Univ. of Munich, became lecturer there in 1960. Honorary Professor Univ. Cologne in 1967, 1968-1971 Professor of Chemistry Univ. of Southern California, Los Angeles, at present Professor at the Technical University Munich. 4-Component peptide synthesis.

Wang. Yu (pp. 161,231, Plate 46) born 1910 in Hangshou, China, he studied in Nanking, Peking and graduated in 1937 in Chemistry at the University of Munich, Germany. After one-year's postdoctoral work with Richard Kuhn at the Kaiser-Wilhelm-Institute for Medical Research in Heidelberg (1938/39) he advanced via Peking to Shanghai where he, as director of the Institute of Organic Chemistry of the Academia Sinica, has been working in different fields of bioorganic chemistry since 1950. Essentially involved in the synthesis of insulin.

Wessely von Karnegg. Friedrich, 1897-1967 (pp. 29,37, Plate 47). After being severely wounded in the First World War, he studied in Vienna from 1919 and graduated there under Franke in 1922. Among his fellow students, we find names such as Hermann Mark and Richard Kuhn. His interest in amino acids and peptides was aroused during the years 1923-1924 spent in Berlin-Dahlem at the Kaiser Wilhelm Institute for Fiber Research where he worked on silk -fibroin. Although he had other interests, he remained faithful to this area of research for over 30 years. At the 2nd Institute of Chemistry of the University of Vienna he was engaged in studies on carbonyl-bisamino acids and collaborated with E. Spath in work on complex natural products of the terpene series. He was named "Privatdozent" in the early thirties. "Extraordinarius" in 1937 and in 1946 invited to be Professor and Chairman of the Institute for Medicinal Chemistry of the University. After the sudden death of E. Spath in 1948, Wessely was appointed as his successor. His last publication from the peptide field appeared in 1957; he died suddenly in 1967. His life outside the laboratory was dedicated to music, he was himself an accomplished pianist, and to the mountains. An artificial leg notwithstanding he skied in the Alps and was an excellent swimmer. An entry in the books of the Polar Institute of Norway in Oslo shows a Wessely Peak on the Magdalena Fjord in the Spitzbergen.

Weygand. Friedrich, 1911-1969 (pp. 70,129, Plate 48). Born in 1911 in Reichelshausen (Upper Hassia) studied chemistry in Frankfurt a. M., moved in 1934 to the Kaiser-Wilhelm-Institut fUr medizinische Forschung in Heidelberg where he took his doctorate with Professor Richard Kuhn (1935) and worked in the Institute until 1940, interrupted by a one-year's stay at Oxford with Sir Robert Robinson (1935/36). He worked in Heidelberg until 1943 when he moved to the University of Strasbourg, then as associate professor to Tiibingen, in 1955 as Full Professor to the Technical University of Berlin, and finally in 1958 as director of the Organic Chemistry Department of the Institute of Technology (now Technical University) in Munich. Beside peptides (trifluoroacetyl derivatives, gaschromatography, mass spectroscopy, p. 129) his interest was also in carbohydrates and heterocyclic compounds.

Wieland Theodor born in 1913 in Munich, he studied chemistry in Freiburg Brsg. and Munich where he received his Dr. phil. in 1937. From 1937 until 1946 he was assistant, (Lecturer 1941), with Richard Kuhn at the Kaiser-Wilhelm/Max-Planck-Institute in Heidelberg. In 1946 he became Prof. at the Univ. of Mainz. Between 1951 and 1968 he was Prof. and Director of the Institute of Organic Chemistry at the Univ. of Frankfurt. After R. Kuhn's death in 1967, he was appointed Director of the Department of Chemistry, later Natural Products, of the Heidelberg Institute until 1981. He is hon. prof. of the Universities of Frankfurt and Heidelberg. His contributions include electrophoresis on paper of amino acids, peptides and proteins, isoenzymes oflactate dehydrogenase (with G. Pfleiderer), mixed anhydride method of peptide synthesis (p. 79) peptides of Amanita mushrooms (p. 211).

274 Appendix

Witkop, Bernhard (pp. 117,209, Plate 49) was born 1917 in FreiburgjBreisgau. He studied chemistry at University ofM unich and there received his Dr. phil. in 1940 (Heinrich Wieland) and became Lecturer in 1946. He became Mellon Fellow at Harvard University in 1947. Instructor and Lecturer 1948-1950; Special Fellow U.S. Public Health Service 1950-1953. He was at Natl. Institute of Health. Bethesda, Maryland USA. from 1953, there the Chief of the Laboratory of Chemistry of the Institute of Arthritis, Metabolic and Digestive Diseases from 1957 until 1987. Witkop, a very all-round scientist (alkaloids, oxidation mechanisms, pharmacodynamic amines, amphibian venoms etc.), in peptide chemistry, studied hydroxyamino acids, non-enzymatic cleavage of proteins (with E. Gross cyanogen bromide cleavage, p. 117), gramicidins.

Woodward, Robert Burns, 1917-1979 (Plate 50). Born in Boston in 1917, he entered Massachusetts Instutute ofTechnology in 1933 and graduated as Ph.D. in 1937. Postdoctoral fellow at Harvard(1937-40). Instructor in Chemistry (1941-1944). Assistant Professor (1944-46), Associate Professor (1946-50), Professor from 1950 until his death in 1979. Nobel Prize in Chemistry 1965, "for his outstanding achievements in the art of organic synthesis". Wood wards reagent (p. 90), synthesis of cephalosporin C (p. 200), polY-IX-amino-acids (p. 37).

Wunsch, Erich (p. 168, Plate 51) born in 1923 in Reichenberg, Bohemia, began studying chemistry in 1941 at the Karls-University, Prague, and after Army service and being a prisoner of war, resumed his studies in Regensburg, Bavaria, in 1946. Graduated Dr. rer. nat. at the Ludwig-Maximilian University in Munich in 1956 and Dr. habil at the Technical University in Munich in 1956. There he was nominated professor in 1973 at the same time he was scientific member of the Max-Planck­Gesellschaft, and director of the department of peptide chemistry at the Max-Planck-Institute for Biochemistry in Martinsried near Munich. Methods of protection in peptide synthesis, synthesis of hormones, author of 2 volumes, Peptides in Houben-Weyl-Miiller's handbook (see p.62) are among his achievements.

Yajima, Haruaki (p. 238, Plate 52) born in Takakarazuka, Japan, in 1925, received his Ph.D. degree as an alkaloid chemist at the Kyoto University in 1956. He then studied peptide synthesis with Klaus Hofmann in the Department of Biochemistry at the University of Pittsburgh until 1962, mainly contributing to the first synthesis of a tricosapeptide with full ACTH activity (p. 164). He returned to Japan in 1962 as Associate Professor at Kyoto University and was promoted to full Professor in 1973. After his retirement in 1989, he moved to Niigata College of Pharmacy as president. Synthesis of a great number of biologically active peptides, also ribonuclease. A are some of his accomplishments.

Young, Geoffrey Tyndale (pp. 95,244, Plate 53). Born 1915. Graduated in Chemistry at the University of Birmingham in 1936. Then moved to Bristol University, working on carbohydrates with E.L. Hirst. In 1938, he received his Ph.D. and was appointed Assistant Lecturer. In 1939-1943, he did war research on explosives at Bristol University. From 1943 to 1945 he was with the British Commonwealth Scientific Office at Washington, U.S.A., exchanging information on war research. In 1947, he was elected Fellow and Tutor in Chemistry, Jesus College, Oxford; 1952, University Lecturer in Organic Chemistry; 1970 Aldrichian Praelector in Chemistry. 1973-1977, Acting Principal, Jesus College, Oxford. 1982, Emeritus Fellow, Jesus College. 1983, O.B.E. (Order of the British Empire). One of the founders of the European Peptide Symposia in 1958.

Zahn, Helmut (p. 161, Plate 54) was born 1916 in Erlangen and studied chemistry and graduated at the Technical University in Karlsruhe (Dr. Ing. in 1940). From 1940 to 1949 he was assistant to Professor El6d at the Institute for Textile Chemistry in Badenweiler, Baden, from 1949-1957 Assistant, Lecturer and Associate Professor at the University of Heidelberg. From 1952-1985 he was Director of the German Institute for Wool Research and in 1960 was appointed full Professor at the Technical University in Aachen. With his team (Plate 54) he was the first to obtain insulin by chemical synthesis.

Zervas, Leonidas, 1902-1980 (p. 46, Plate 55) was born in Megapolis in the Peloponese, Greece. He studied chemistry at the University of Athens and then in Berlin where, in 1926, he received his Ph.D.

Appendix 275

degree. The experimental work leading to this degree was carried out in Dresden at the Kaiser Wilhelm Institute and was gruided by its director, Max Bergmann (see p. 44). After graduation, Zervas remained in Dresden as research associate; a few years later he was promoted to Head of the Organic Chemistry Section and then to Associate Director of the Institute. After the resignation of Bergmann in 1933, Zervas stayed in Dresden to complete the ongoing studies but a year later he followed Bergmann to New York City to participate in his research at the Rockefeller Institute.

In 1937 Zervas returned to Greece where he was appointed Professor at the University of Thessaloniki. Two years later he accepted an invitation to the University of Athens, where he remained, even after his retirement in 1968. He became a member of the Academy of Athens, was named, in 1964, Secretary ofIndustry and was one of the initiators of The National Hellenic Research Foundation. In spite of such new responsibilities he continued to be active in the laboratory until the end of his life. His carbobenzoxy group and the consequences for peptide chemistry are discussed in chapter 3.

Author Index

Boldface page nwnbers refer to illustrations

Abderhalden, Emil 3, 31,34, 35, 44, 51, 114-118, 235, 250, 264

Abel, 1.1. 153, 157 Abraham, E.P. 200, 243 Acher, Roger 232, 245 Acs, G. 207 Akabori. Shiro 116, 117,238,250,264 Albaricio, F. 240 Albertson, N.F. 65,83 Amaral, M.J.SA. 240, 244 Amiard, G. 232 Amiradzibi, S. 14 Anantharamaiah, G.M. 236 Anastasi, A 185, 238 Anderson, G.W. 82,95,143,246 Anfinsen, C.B. 237,246 Antonov, V.K. 247 Aoyagi, H. 239 Arens, I.F. 88, 242 Arnon, R. 237 Arns~H.R.V. 199 Arold, H. 235 Aston, F.W. 128 Atherton, E. 244 Audrieth, L.F. 154

Baeyer, A 25, 32, 33 Bajusz, S. 164, 236 Balaspiri, L. 236 Balbiano, L. 24 Ballard, D.G.H. 40 Bamford, C.H. 40, 41 Banting, F.G. 153, 157,230 Barany, G. 108, 246 Barber, M. 130 Barbieri, J. 6 Barger, George 7, 15, 154, 193 Barton, MA. 230 Bartos, I. 232 Bauer, W. 242

Baumann, E. 5 Baumert. A 235 Bayer, Ernst 54, 55, 234, 250, 264 Bayliss, W.M. 136 Beecham, AC. 229 Begg, G. 229 Begg, C. 119 Behrens, O.K. 15, 245 Belleau,B. 91,230 Ben-Ishai, D. 64, 237 Benedetti, E. 238 Benoiton, L. 96, 230, 244 Berger, A. 39, 64, 237 Bergmann, Max 3,4, 44ff, 68, 114, 117,

118,138,154,195,235,244,264 Bernardi, L. 238 Berse, C. 230 Berzelius, J. 5, 228 Best, Charles H. 153, 157, 230 Beyennan, H.C. 243 Biemann, Klaus 128, 264 Birkofer, Leonhard 69 Birr, Ch. 67,233 Bishop, C.J. 222 BI8ha, Karel 122,231,250,264 Blake, J. 246 Bloch, Ignaz 44, 125 Bloemhoff, W. 243 Blombll.ck, E. 241 Blombll.ck, B. 241 Blout, Elkan R. 39,41, 124, 203, 209, 230,

245 Blumberg, P. 114 Blundell, T.L. 244 . Bodanszky,~os 85,145,236,246,264 Boissonnas, RA. 81, 85, 145, 185, 245 Boon, P.I 243 Borin, G. 237 Borsook, H. 57 Bosisio, B. 238 Bossert, H. 242 Botes, D.P. 222

278 Author Index

Boucher, R. 230 Bourgois, A. 6 Bouveault, L. 7 Braconnot, H. 5 Bragg, W.L. 131 Bragg, W.H. 131 Brand, E. 205 Brandenburg, D. 234 Brazhnikova, M. 203 Bremer, H. 234, 262 Brenner, Max 37, 58, 93, 98, 196, 242,

251,265 Bricas, E. 232, 235 Brill, R. 3 Brinkhoff, O. 262 Brockmann, Hans 38, 117, 118,201,224,

251,265 Brown, IC. 168 Bruckner, Victor 41,236,251,265 Brunfeldt, K. 231 Buckingham, D.A. 239 Buku, A. 246 Bumpus, P.M. 182, 246 Bunsen, Robert 33 Bystrov, V.P. 247

Calm, R.S. 10 Cahours, A. 5 Calderon, I 229 Callahan, P.M. 95,246 Carlsson, L. 241 Carpenter, P.H. 245 Carpino, L.A. 65, 70, 107,246 Carr, F.H. 193 Carter, H.E. 7 Cash, W.D. 245 Castro, B. 92 Ceprini, M.Q. 85 Cham, E. 198 Chamberlam, IW. 68 Chambers, D.C. 121 Chandramouli, N. 237 Chang, W.C. 231 Chantrenne, H. 77 Chen, P.M.P. 230 Cheng, L.L. 231 Chi, A.H. 231 Chillemi, F. 238 Chimiak, A. 240 Chipens, OJ. 248 Chorev, M. 237 Chu, S.Q. 231 Chung, D. 246 Claisen, L. 90

Clauson-Kaas, N. 19 Clemo, O.R. 155 Cole, S.W. 6 Colombo, R. 238 Consden, R. 14, 52, 205 Copp, D.H. 170 Corey, Robert B. 41, 132 Coy, D.H. 246 Craig, Lyman C. 55, 56, 137, 139, 155,

194,203,245,252,265 Cramer, E. 6 Cuatrecasas, P. 237 Curtis, R.W. 20 Curtius, Theodor 24-31, 32ff, 77, 79, 145,

265

Dale, J. 239 Dale, H.H. 137, 193 Das,B.C. 129,232 Day, A.R. 85 de Castiglione, R. 238 de Meyer, I 157 de Wahl, H.A. 183 Deber, C. 230 Deisenhofer, Johann 132 Denkewalter, R.O. 41 Dessaignes, V.D. 5 Determann, H. 55, 233 Di Bello, C. 237 Diels, Otto 34 Dittmer, W. 6 Dixon,O.H. 160,230 Doleschall 89 Donohue, J. 132 Dormoy, J.R. 232 Doty, P. 122 Drabarek, S. 240, 245 Drechsel, E. 6 du Vigneaud, V. 15, 44, 45, 64, 71, 137-

152, 153ff, 199, 228-232, 237, 245 Du, Y.C. 230,231 Dubos, R. 203, 207 Duisberg, Carl 32, 33 Durieux, C. 232 Dyckes, D.P. 245

Eberle, Alex 241 Edkins, J.S. 136 Edman, Pehr V. 118, 119, 139, 155, 229,

240, 251, 265 Ehrlich, Pelix 7 Ellinger, A. 6 Elliot, D.P. 244

Emery, AR. 82 Erickson, B.W. 245 Erlanger, B.F. 205 Erlenmeyer, E. 5, 6 Ersparner, Vittorio 166, 184, 185, 238,

252,266 Euler, K.E. 37

Fairlarnb, AH. 18 Faraday, M. 1 Farrington. J.A. 85, 244 Farthing 36,40 Fasman, G.T. 122 Faulstich, H. 217,233 Ferger, M. 245 Fennandjian, S. 232 Finn, F. 246 Fischer, Emil 2, 4, 6, 10, 13, 27-31, 32ff,

44,46,53,54,67,69,77,235,266 Fischer, H.O.L. 33 Fischer, Laurenz 33 Fischer,Otto 33 Fin, P.S. 245 Fiwne, Luigi 220 Flarnand, C. 6 Fleming, Alexander 198 Fletcher, G.A. 244 Flodin, Per 55,241 Florey, H.H. 198 Flouret, G. 245 Folch, Georg 240 Fontana, A. 237 Ford, W.W. 211 Foster, G.L. 114 Fourneau, E. 2 Fox, Sidney 38 Fraenkel-Conrat, Heinz 47, 57, 60 Frank, V.S. 78 Frankel, M. 38, 237 Freudenberg, Karl 46 Fric,l. 231 Fridkin, M. 237 Friedmann, E. 5 Friedrich, Walther 131 Fromageot, P. 232 Fromageot, C. 117, 232 Fruton, Joseph S. 3, 47, 56, 61, 246, 252,

266 Fuchs, H. 36, 40, 49 Fujii, Nobutaka 170, 239 Fujino, Masahiko 239 Fukuda,K. 161 Funk, K.W. 247

Gaddum, J.H. 184 Galpin, 11. 244 Gause, Georgyi 203 Gebert, U. 221

Author Index 279

Geiger, Rolf 87,93, 110,233,234,253, 266

Gelling 157 Gerlach, H. 203 Gevers, W. 208 Gibbons, W. 244 Gierasch, L. 246 Gil-Av, E. 55 Gillessen, D. 245 Gilon, C. 237 Giralt,E.240 Glass, 1. 245, 246 Goffinet, B. 232 Gold, V. 82 Goldblatt, H. 181 Goodman, Murray 246, 266 GlSrdeler, J. 68 Gordon, AH. 205 Gordon, M. 14,52, 85 Gorup-Besanez. E.v. 6 Goutarel 224 Grassmann, Wolfgang 56, 233 Gray, W. 116 Greenstein, J.P. 7 Gregory, RA. 136 Grimaux, E. 2, 24 Gross, Erhard 62, 117, 222, 246, 267 Gross, R.E. 48 Griltzmacher, H.F. 129 Grzonka, Z. 240 Guillemin, Roger 172, 246, 267 Gulevitch, W. 14 Gurd, F.RN. 245 Gut, V. 231 Gutte, B. 245 Guttmann, S. 242

Habermann, E. 186 Hagenmayer, H. 234 Hallermayer, R. 211 Han, G.Y. 70, 107 Hansen, Bruno 231 Harding, V.J. 52 Hardy, G.W. 244 Hardy, P.M. 243 Harington, Charles R. 15,65, 141, 154 Hartmann, F. 79 Hassal, C. 244 Hauptmann, J.A. 133 Havinga. E. 243

280 Author Index

Heartley, B.S. 116 Hedin, S.O. 6 Helferich. Burckhardt 13,67,68 Hermann, Peter 235 Hess, O.P. 88 Heymens-Visser, O. 243 Heymes, R. 232 Heyns, K. 129 Hirs, C.H.W. 51 Hirschmann, Ralph F. 41, 247, 267 Hiskey, R.O. 73, 246 Hlavacek, J. 231 Hoagland, M. 207 Hodges, R.S. 230 Hodgkin, Dorothy C. 159, 244, 253, 267 Hofmann, Klaus H. 38, 41, 163, 245, 267 Hofmann, A. 194 Hofmeister, Franz 2, 253, 267 Holley, Robert W. 155, 245 Holst 68 Holzwart, O. 122 Honzl,1. 41, 231 Hoogerhout, P. 243 Hope. D.B. 244, 245 Hopkins, F.O. 6,15 Homer, Leopold 26 Hlirnle, S. 234 Houghten, RA 111,246 Hruby, Victor J. 245, 246, 267 Hsing, C.Y. 231 Hsu, J2. 231 Hu, S.C. 231 Huang, W.T. 231 Huber, Robert 132 Huffmann, O.W. 247 Hughes, I 187 Huguenin, R. 242 Hunkapiller, M.W. 120

Ingold, C.K. 10 Iselin, B. 242 ltoh. Masumi 239 Ivanov, V.T. 215, 247, 248 Ivanovics, O. 41, 236 Izdebski, J. 240 lzumiya, Nobuo 207,239

Jacobs, JJ\. 55, 194 Jaeger, E. 233 Jakubke, H.D. 61, 235 James, A.T. 54 Jaquenoud, PA 242 Jarvis, D. 243, 245

Jensen, Hans 153 Jentsch. J. 186 Jeschkeit, H. 235 Jiang, R.Q. 230 Joaquina, M. 240 Johansen, J.T. 60,231 Jlihl, A. 245 Jones, D.S. 244 Jorpes, IE. 136, 166, 167, 169, 241, 254,

268 Jost, K. 146,231 Jung, O. 234

Kader, A.T. 70 Kaiser, E.T. 245 Kajtar, M. 236 Kamber, B. 73, 242 Kamm, O. 137 Kann, E. 117 Kapfhammer, J. 48 Kappeler, H. 242 Karle, Isabella L. 133, 215, 246, 268 Karle, Jerome 133 Katchalski, Ephraim 38, 39, 40, 237, 254,

268 Katsoyannis, P.O. 73, 152, 160, 161, 235,

245,246,255,268 Katzir see KatchaIski, E. Kaufmann, H.P. 216 Ke, L.T. 231 Kekule, A.v. 1 Kemp, D.S. 97,245 Kendrew, J.L. 5, 132 Kenner, O.W. 81, 85, 95, 230, 244, 255,

268 Kent, S.B.H. 245 Kerling, K.E.T. 243 Kessler, H. 127, 216, 234 Khan, SA 236 Khorana, H.O. 88 Khosla, M.C. 182, 246 Kidd, D.AA 69 King, F.E. 69 Kiryushkin, A.K. 247 Kisfaludi, L. 85, 236 Klausner, Y.S. 237 Kleinkauf, H. 208 Klostermeyer, H. 234 Knippling, Paul 131 Knorr, Ludwig 33 Knowles, R.I 244 Koenigs, W. 32 Kofod, H. 231Kolbe, H. 25 Klinig, WA 234

Kemdg, VV. 55,87,93,110,233,234,253 Kopple, K.D. 246 Kornet, M.J. 103, 104 Kossel, A. 6, 48 Kostansek, E.C. 221 Kosterlitz, H.VV. 187 Kovacs, J. 85, 96 Kovacs, K. 236 Kraut, K. 79 Kuhn, Richard 48, 49 Kung, Y.T. 231 Kunitz, M. 56 Kunz, H. 233 Kupryszewski, G. 240 Kurahashi 208

Laland, S.G. 208 Laschi, R. 220 Laskowski, M. 58 Latham, P.VV. 1 Laursen, RA. 120 Lebl, M. 231 Lederer, Edgar 48, 129, 232, 255, 268 Lehn, J.M. 203 Lempert 89 Lentz, K.E. 182, 246 Leplawi, M.T. 240 Letsinger, R.L. 103, 104 Leuchs, Friedrich 35 Leuchs, Hermann 6, 35f, 255, 268 Leuchs, Georg 35 Lewis, H.B. 153 Li, Choh Hao 231,246,256,268 Liberek, B. 240 Liebig, J.v. 5 Light, A. 245 Likiernik, A. 5 Lilienfeld, L. 24 Limpricht, H. 5 Lindeberg, G. 241 Lipmann, Fritz 155,207,208,245,268 Lipp, A. 5,6 Loew, Oscar 1 Loffet, A. 229 Loh, T.P. 231 Loquin, R. 7 Losse, G. 234 Low, M. 236 LUbke, K. 234 Lucente, G. 196,238 Lundell, E.O. 245 Lynen, Feodor 78, 208, 211

Author Index 281

Maassen van den Brink, VV. 243 MacLean, R.M. 52 Magee, M.z. 38 Magendie, F. 1 Malek, G. 91 Mancheva, I. 229 Manning, M. 151, 245 Marchiori, F. 237 Marcussen, Jan 231 Marglin, A. 161, 245 Markovnikov, VV. 6 Marquarding, D. 233 Marquet, A. 232 Marsch, R.E. 132 Marshall, G.R. 108, 245, 246 Martin, A.lP. 14, 52, 54, 114, 205, 243,

256,269 Martinez, Jean 232 Marvel, C.S. 153 Matsueda, R. 239 Mazur, R.H. 247 McKay, F.C. 65 Mead, T.H. 15, 65 Medzihradszky, K. 236 Medzihradszky-Schweiger, H. 236 Meienhofer, J. 62, 81, 233, 245, 262 Meister, A. 18, 245 Merrifield, R.B. 67, 104-112, 161, 213,

245,247,269 Meyer, C.E. 7 Meyer, Victor 33 Michel, Hartmut 132 Michl, H. 229 Miekeley, A. 117 Miller, J.G. 85 Minkowski, O. 157 Mitchell, A.R. 245 Mitin, Y. 247 Miyazawa, T. 123,124 Mladenova-Orlinova, L. 229 Montecucchi, P. 238 Moore, Stanford 48, 50, 51, 61, 138, 155,

245,269 Moore, C. 201 Morley, 1 244 M6rner, KA.H. 5 Moroder, L. 233, 237 Mueller, lH. 7 Mukaiyama, Teruaki 98, 239, 247 Mulders, G. 1 Munekata, E. 218,233,239 Munk, E.M. 90 Muramatsu, Ichiro 238 Murlin, J.R. 44, 153 Murti, V.V.S. 237, 245

282 Author Index

Musso, H. 38 Mutt., Viktor 136, 166-169,241, 254, 269 Mutter, M. 234, 242 Muzalewski, F. 240

Nager, U. 20 Natarajan, S. 237 Nefkens, G.H.L. 70, 85, 243 Nestor, JJ. 245 Nesvadba, H. 229 Neumeister, R. 2,6 Newton, G.G.F. 200, 243 Nicolaides, E.D. 183 Niedricb, N. 234 Niemann, C. 3 Niu, C.I. 231 Nivard, R.IF. 243 Noble, R.L. 246 Northrop, IH. 56 Nutt., R.F. 247

Obermeier, R. 234 Offord, R.E. 242, 244 Okawa, K. 238 Okuda, T. 234 Ondetti, Miguel A. 183, 246, 256, 269 Osato, R.L. 82, 141 Ovchinnikov, Y A. 202, 215, 247, 248,

256,270

Pacsu, E. 38 Page,I.H. 182,246 Panneman, H.J. 242 Paolillo, L. 238 Pasteur, Louis 198 Patchomik, Abraham 68,237,254,270 Patel, 0.1 215 Pauling, L. 41, 132, 257, 270 Pedersen. CJ. 203 Pedone, C. 238 Pedroso, E. 240 Peggion, E. 237 Penke, B. 236 Perseo, G. 238 PerulZ, M.F. 5, 132 Photaki,Iphigenia 37,73,235,242,245,

257,270 Piche, L. 230 Pierce, IG. 245 Pietta, G. 108,238 Pine, N.W. 15 Pinnen. F. 238

Piria, R. 6, 15 Pitt-Rivers, R.V. 141 Piutti, A. 6 Plattner, PA. 19,20 Pless, J. 85, 242 Poduska, K. 231 Popenoe, E.A. 245 Porath, Jerker 55,241 Pravda, M. 231 Pre1og, V. 10,203 Pressman, B.C. 201 Prox, A. 129, 233 Purcell 125 Pyman, F.L. 6

Rachele, J.R. 245 Ragnarsson, U. 241 Ramachandran, GN. 236 Ramachandran, J. 246 Ramage, R. 244 Reichert., E. 78 Ressler, C. 139, 245 Richardson, W.L. 206 Ridge, B. 243 Riniker, B. 73, 242 Rittel, W. 242 Rittenberg, D. 114 Ritthausen, H. 6 Rivier, J. 246 Robinson, Robert 154 Robiquet., P. 5 Rocchi, R. 237 Roeske, R.W. 245 Romeo, A. 196 Roques, B.P. 232 Rose, W.C. 7, 153 Roser, K.L. 196 Rothe, Manfred 40,196,207,234,270 Rudinger, Josef 41, 145, 146, 147, 152,

155ff,231 Ruhemann, S. 51, 113 Ry~H.Norman 38,243,258,270 Rzezsotarska, R. 240

Sachs, H. 205 Said, Sl. 168 Sakakibara, Shumpei 67, 107, 145, 167,

169, 238, 258, 270 Sakarellos, A. 235 Sakarellos, C. 235 Sakarellos-Daitsiotis, M. 235 S~ E. 185, 242

Sanger, Frederick 2, 115, 116, 138, 155, 158,159,228,258,271

Sarges, R. 209 Sato, M. 238 Sawyalow, W.W. 57 Scatturin, A. 237 Schaal, E. 24 Schally, AJKkew V. 172,271 Schattenkerk, C. 243 Schiff, H. 24 Schiller, P.W. 164, 230, 241 Schinner, R.H. 5 Sch16gl, K. 229 Sclunidt, Ulrich 225, 234 Sclunidt-Kastner, G. 201 Sclmabel, E. 65, 234, 262 Schlin, I. 236 Schlinheimer, Rudolf 46, 64 Schramm, C.H. 37 Schramm, G. 38 Schr6der, E. 234 Schulz, G.E. 5 Schulze, E. 5,6 SchUtzenberger, P. 2, 6, 24 Schwab, G.M. 49 Schwarz, H. 182 Schwyzer, Robert 65, 68, 84, 164, 205,

207,230,241,258,271 Scoffone, Ernesto 237,259,271 Scott, D.A. 230 Sealock, R.R. 146 Sela, M. 40, 237 Sheehan Jolm.C. 69, 78, 88, 90, 108, 199,

200,206,245,247,259,271 Shemyakin, M.M. 20,202, 247, 248, 259,

272 Sheppard, R.C. 244 Sheraga, H. 246 Shi, P.T. 231 Shiba, Tetsuo 224, 238, 259, 272 Shimonishi, Y. 107, 145, 238 Sieber, P. 68, 73, 164, 205, 207, 242 Siemion, IZ. 240 Sigmund, F. 37 Shnrnonds, S. 245 Sivanandaiah, K.M. 236 Sj~berg, B. 241 Skeggs Jr., L.T. 182,246 Skroka, W. 234 Sluyterman, LAE. 38 Smeby, R.R. 182, 246 Smith, Emil L. 56 Smith, P.W.G. 38 Snell, E.E. 114 S6rensen, S.P.L. 4, 6

Author Index 283

Sorm, F. 155 Spackman, D.H. 51 Spangenberg, R. 72 Sparrow, J.T. 246 Spatola, AF. 246 Spies, I.R. 121 Staab, HA 91 Stahl, E. 53 Stammer, I. 246 Starling, E.H. 136 Staudinger, H. 4 Stedman, J. 245 Steglich, W. 98, 233 Steiger, E. 6 Stein, William H. 4,48,50, 51, 61, 138,

155, 244, 272 Stelakatos, G.C. 235 Stevens, C.L. 90 Steward, J.M. 245 Stewart, F.H.C. 229, 245, 246 Stirling, C.J. 70 Stirpe, F. 220 Stix, W. 115 Stoev, S.B. 229 Stoll, Arthur 193 Stouffer, J.E. 245 Strecker, A 6 Studer, R.O. 207, 242, 245 Svedberg, T. 4 Swan, J.M. 228, 245 Synge R.L.M. 52, 114, 205, 243, 260, 272 Szelke, M. 236, 244

Tam, I.P. 245 Tamburro, AM. 237 Tamussi, P A. 238 Tang, K.L. 231 Tanret, Ch. 193 Tasclmer, Emil 239, 260, 272 Tatemoto, H. 241 Tesser, G.1. 85, 243 Theodoropoulos, D. 71,235 Thomas, D.W. 232 Thompson, E.O.P. 228 Thunun, G. 38 Tiselius, Arne 4, 49 Titlestad, K. 239 Tobschirbel, A 216 Tolle, I.C. 247 Tomatis, R. 237 Tometsko, A 161 T6morkeny, E. 236 Tonelli, A.E. 215 Toniolo, C. 237

284 Author Index

Tracy, HJ. 136 Trasciatti, D. 24 Tregear, G.W. 111 Trippet, S. 139 Troensegaard, N. 3 Trudelle, Y. 232 Tsou, L.C. 230 Tswett, M.S. 49 Tuppy, H. 140,229 Turba, Fritz 49 Turner,1.M. 85 Tzougraki, C. 235

Udenfriend, S. 52,62 Ueki, M. 239 Ugi, Ivar 99, 233, 273 Urry, D.W. 209

Vajda, T. 236 van Binst, G. 229 van Nispen, I.W. 243 van Rietschoten, P. 240 van Rietschotten, I. 232 van Slyke, D.D. 114 Vaughan Ir., I.R. 81, 82, 141, 246 Vauquelin, L.N. 5 Vavrek, R.I 245 Veber, D.F. 72, 247 Velluz, L. 71 Verdini, S. 238 Verhart, C.G.I. 243 Vidali, G. 237 Virtanen, A.I. 59 Vlasov, G.P. 247 Vogler, K. 242 von Bunge, Gustav 34 von Euler, U.S. 184 von Hofmann, August Wilhehn 33 von Laue, Max 131 von Mering, I. 157

Wade, R. 244 Waksman, S.A. 224 Waldsclunidt-Leitz, Ernst 49, 56 Waley, S.G. 18,41 Walter, R.W. 245 Wang, S.S. 108 Wang Yu 73,231,260 273 Warburg, Otto 29 Wardlaw, A.C. 160, 230 Wasteneys, H. 57 Weber, U. 234 Weigele, M. 52

Weigert, F. 6 Weisz, E. 236 Wenger, R.M. 211 Wessely von Karnegg, F. 29, 37, 39, 40,

41, 229, 260, 273 West, H.D. 7 Weygand, Friedrich 54, 64, 97, 129, 233,

234,261,273 Wieland, Heinrich 211, 212 Wieland, Theodor 7,37,53,55,78,79,80,

84, 233, 239, 273 Wieland, Ulrich 211 Wilchek, M. 237 Williams, N.W. 244 WillsWter, Richard 6, 56 Wilson, E.I 38 Winitz, M. 7 Wintemitz, F. 232 Winterstein, E. 6 Wintersteiner, Oskar 153 Wissmann, H. 234 Witkop, Bernhard 117,209,212, 246, 261,

273 Wolff, L. 6 Wollaston, W.H. 5 Wohnan, Y. 237 Woodruff, H.B. 224 Woodward, Robert B. 37, 90, 200, 245,

261,274 Wooley, D.W. 245 Wrinch, Dorothy 3 wUnsch, Erich 56, 62, 71, 72, 168, 233,

261,274 Wilthrich, K. 242 Wyckhoff, R.W.G. 132

Yajima, Haruaki 170,238,262,274 Yamashiro, D. 245, 246 Yanaihara, C. 238 Yanaihara, N. 238 Yich, Y.H. 231 Yiotakis, A.E. 235 Young, Geoffrey T. 95,262,274

Zabel, R. 234, 262 Zachau, H.G. 207 ~Hehnut 72,73,161,229,262,274 Zanotti, G. 197, 238 Zaoral, M. 231 Zemplen. G. 235 Zervas, Leonidas 44, 46, 47, 61, 65, 71,

73,154,235,257,263,274 Zuber, H. 242

Subject Index

Page numbers in italics refer to figures and formulas

ACE (angiotensin converting enzyme) 181-183, 186

- inhibitors 246, 270 Acetamido-methyl group 72 Acetate, active 78 Acetic anhydride 79 Acetic acid 110 - -, activated 208 Aceturic acid 25, 79 Aceturyl peptides 26 Acetyl chloride 29, 79, 80 S-Acetyl coenzyme A 78 N-Acetylglycine 25, 46 - ethyl ester 46 N-Acetylglycyl-N-acetylglycine ethyl ester

46 N-Acetylleucyl-proline 128 N-Acetylpeptides 129 - esters 129 Acetylphenylalanylalanylglycine amide 56 Acetyl phosphate 77, 78 Acid alumina column 50 Acid azides 77 Acid-labile protecting groups 67 Acidolysis 66, 68, 105, 233 ACfH 163, 188, 236, 241, 266, 274 -, human, amino acid sequence 163 -, stepwise chain-lengthening with active

esters 164 Actin filaments, stabilization, phallotoxin

218 Actinomyces 203 Actinomycins 120,224,224,265 Actin, phallotoxinslvirotoxins 218 O-Acyl-N-dialkyl-hydroxylamines 86 Acyl amino acid thiophenyl esters 84 - - -/trimethylacetic acid 83 O-Acylaminoacyl-piperidines 86 Acylimidazoles 91 O-Acylisourea derivatives 89-94 Acyl migration 90 N-Acylnitroarginine 85

Acyloxyphosphonium salts 92 Acyloxyphosphonium compounds 247 N-Acylserine 85 N-Acylseryl-glycine amide 197 N-Acylthreonine 85 Acyltripeptide methylester, MS 129 N-Acylureas 93 -, derivative 90 Adenosine triphosphate (ATP) 77,208 S-Adenosyl-methionine 211 Adrenal gland 163 Adrenocorticotropin (ACTH) 163, 188,

236, 241, 266, 274 Affinity binding, enzymes 57 Affinity labeling, hormone receptors 241 Alamethicin 210f Alanine 6 -, NMR 125 -, ~-oxindol- 217 -, X-ray crystallography 132 Albumin 1 Alburninoids 1 Albumoses 2 Alkaloids, ergot 3, 193f, 265 -, neurotoxic 222 -, peptides 224, 234 -, strychnine 36 Alkyl carbonic acid mixed anhydrides 81 Alkylchlorocarbonate (chloroformate) 80 Alkylesters, saponification 69 Allyloxycarbonyl group 67 Alytesin 186 Amanin 219 Amaninamide 220 Amanita research 233,273 Amanita bisporigera 217 Amanita phalloides 211, 212, 216, 217,

219 Amanita tenuifolia 217 Amanita virosa 217 Amanitatoxin 211 Amanitin 212,217-221

286 Subject Index

Amanullin, FAB mass spectrum 131,131 Amatoxins 217, 219f Amberlites 50 Amines, tertiary 81 Amino acid esters, peptide bond fonnation

58 Amino acid chloride hydrochlorides 37 Amino-protecting group, easily removable

29 Amino acids, analyzer 51,269,272 -, bifunctional 31 -, C-tenninal 116 -, chromatography 49f,233 -, chronology 5 -, derivatization 113 -, dennorphin 186 -, a-disubstituted 240 -, functional side chains 11 -, hindered 81 -, one-letter abbreviations 7, 7 -, posttranslational modification 9 -, purification 113 -, separation of enantiomeric 234 -, synthesis 272 -, thioether 222,223 -, three-letter abbreviations 7 S-Aminoacyl CoA 78 Aminoacyl copolymer 111 S-Aminoacyl cysteamines 78 - cysteines 78 Aminoacyl insertion 196,197 L-n-Aminoisobutyric acid 210 Aminolysis, cyanomethyl esters 84 -, methyl esters 84 - reaction, catalysis 87 -, thiophenyl esters 85 6-Aminopenicillanic acid 198, 200 Aminopeptidases 150 Aminothioic acids 37,78 Ammonolysis 105, 108 -, methyl esters 84 -, phenyl/vinyl esters 85 Amphibians, skin peptides 166, 185f Ampicillin 198 Anchoring 104, 108 - ester bond, cleavage 105 Angiotensin 77, 1m, 18lf, 188, 243, 244 -, analogs 182, 243 -, antagonists 182 -, converting enzyme (ACE) 181, 186 -, - -, inhibitors 183, 246 -, release 183 Angiotensinogen 182 Angiotensin-renin system 244

Anhydrides 79ff Anhydrides, mixed 69, 78-87, 142,233,

242 -, -, acyl amino acidsltrimethylacetic acid

83 -, -, acyl amino acids/sulfuric acid 81 -, -, alkylcarbonic acid 81 -, -, disproportionation 83 -, -, ethylcarbonic acid 91 -, -, intermediates 79 -, -, isobutylcarbonic acid 81 -, -, isovaleric acid/acylamino acid 82 -, -, phosphoric acid 92 -, -, procedure/method 213, 219, 273 -, -, sulfuric acid 244 Anhydrides, symmetrical 79, 83, 84, 89,

94,108,111 Anhydrocyclols 196 Aniline 37, 57, 61 2-Anilinothiazolin-5-one 119, 119 Antamanide (anti-amanitatoxin) 122, 129,

212f,212 -, alkali-metal complex 216 -, analogs 214 ' -, CD spectra 214, 215, 122 -, Li+ complex 215 -, synthesis 213 -, X-ray diffraction analysis 133, 214, 215 Antiarrhythmic action, oxytocin 149 Antibiosis 198 Antibiotic activity, ion transport, valino-

mycin 202 Antibiotics, from Bacillus brevis 204 -, penicillins 154 -, peptides 198f, 242 -, synthesis 272 Antimicrobial spectra 154 Arginine 6, 48, 49, 62, 107 Argon gas 130 Arrhythmia, digitalis-induced 149 S-Arylcysteine 17 Arylesters 85 S-Arylglutathione 17 Asparagine 5, 62, 66, 67, 109, 142 Aspartame 165,244 Aspartic acid 2, 6, 48, 114 Aspergillus niger 20 ATP 77,208 -, X-ray crystallography 132 Atrial peptides 189 Azacyclols 196,196 Azide procedure 145 Azlactones 44,45,96, 154

Bacillus anthracis 41 Bacillus brevis 203 Barium hydroxide 48 Bates'reagent 92 Benzotriazolyl-N-oxytridimethylaminophos-

phoniumhexafluoro phosphate 92 Benzoylarginine ethyl ester 60 Benzoylaspartyltyrosine amide 56 Benzoyl chloride 80 Benzoyldileucine anilide 57 I-Benzoylglucose 46 Benzoylglycine peptides 26 Benzoylglycine anilide 57 Benzoylglycine 57 Benzoylglycylglycine 24, 32, 79 Benzoylhexaglycine 27 Benzoylleucine 57 Benzoyllysine amide 56 Benzoylpentaglycine ester 26 N-Benzoyl peptides 25 Benzoyl-polyglycines 32 Benzyl alcohol 96 Benzylation, thiol groups 141 Benzyl bromide 64 Benzyl chlorocarbonate 62 S-Benzylcysteine 96, 97 Benzyl esters 66, 142, 202 - linkage 107 Benzyl ethers 66 Benzyl groups 46, 71 S-Benzyl group 107 Benzyl mercaptane 96 Benzyloxycarbonyl (carbobenzoxy) group

47,63,97,164,264 - -, reduction, sodium in liquid ammonia

142 - derivatives 104 Benzyloxycarbonyl-L-proline 142 Benzyloxycarbonyl-L-Ieucylglycine ethyl

ester 141 N-Benzyloxycarbonyl-S-benzyl-L-cysteinyl-

L-tyrosine 141 Benzylpenicillin 154 O-Benzylserine 96 Benzyltrifluoroacetate 64 Biogenetic engineering, insulin 163 Biphenylisopropyloxycarbonyl group 107 Biphenylylpropyl-2-oxycarbonyl (Bpoc) 66 N-Bisaminoacylamides 196 Biuret base/reaction 2, 30 Blocked nonapeptides 143 Blocking groups 235, 275 - -, acid-sensitive 242 - -, acidolytic cleavage 237

Subject Index 287

- -, Boc 68, 105, 107 - -, tert-butyl based 107 - -, ~-halogenethyl 240 - -, photo-sensitive 270 - -, selectively removable 239 Boc group (tert-butyloxycarbony 1), blocking

65, 68, 97, 105, 107, 169 Boc-fluoride 65 Bombesin 186 BOP (benzotriazolyl N-oxytridimethyl­

aminophosphonium hexafluorophos­phate), coupling reagent 92, 232

Bothrops jararaca 186 Bradykinin 183f, 185, 186, 235, 244 - antagonists 184 -, 6-g1ycine- 184 Bromelain 60 Bromine water 138, 144 Bromoisocaproyl chloride 31 Bromoisocaproyltriglycine chloride 31 a-Bromopropionic acid 29 Bunte salts 72 Bursin 189 sec-Butyl chlorocarbonate 81 tert-Butyl esters, preparation 240 tert-Butyloxycarbonyl group see Boc

group S-tert-Butylthiocysteine 72 tert-Butyltrifluoroacetate 95

Caerulein 166, 188, 238 Calcitonin 169, 170f, 246 - synthesis, disulfide formation 170 Calcium hydroxide 48 Captopril 183 Carba analog, oxytocin 147 Carbamoic acid 64 Carbanion 95 -, resonance-stabilized 96 N-Carbethoxy peptides 29 N -Carbethoxyphthalimide 243 Carbobenzoxy group 44f, 60, 72 Carbodiimides 83,84,87,88,90,94, 109,

200, 206, 238 -, polymeric 237 -. water-soluble 169 a-Carboethoxy-a-benzyloxypropionyl

residue 194 N-Carboethoxyamino acid chlorides 35 N-Carbonic acid 63 Carbonium ion 66 Carbonyl-bisamino acids 273 Carbonyldiimidazole (CDI) 91

288 Subject Index

Carboxamide,from benzhydryl resin 109 Carboxamide group, dehydration 93 N-Carboxyamino acids 36 N-Carboxyanhydrides 35,229 'Y-Carboxyglutamic acid 9 Carboxyl group, activation 89,95 Carboxylic acid hydrazides 26 Carboxypeptidases 60, 161, 162, 184, 231 Carnosine 14,64 -, synthesis 63,64 Carotinoids 49 Casein 1,28 Catalysis, bifunctional 243 Cathepsin 60 CD (circular dichroism) 120, 121 CDI (carbonyldiirnidazole) 94 Cephalosporanic acid 199 - -, 7-amino- 199, 200 Cephalosporins 198f, 243 -, synthesis 274 -, thiazine ring 200, 201 Cephalosporium acremonium 199,200 Cerebellin 189 Cerebellum-specific peptide 188 Cerebrogastrointestinal honnonal peptides

189 Chain lengthening, stepwise 145 Chain tennination 110 Channel-fonning peptides 267 Chemical shifts 125 Chimeric protein 162 Chiral compounds 121 Chiral phase 55 Chiral purity 93,96,99, 169,230 Chiroptical methods 122 5-Chloro-8-hydroxyquinoline 86 Chloroacetonitrile 84 2-Chlorobenzyl esters 107 2-Chlorobenzyloxycarbonyl group 107,169 Chlorophylls 49 Cholecystokinin (CCK) 165f, 168, 188,

238 -, intestinal extracts 166 -, sulfate ester in tyrosine 166, 167 Cholecystokinin-pancreozymin (CCK-PZ)

136, 166, 241 Chromatography 48f, 114, 119,269 -, affinity 110, 237 -, gas 113, 273 -, gel 55 -, gel penneation 170,241 -, HPLC 54 -, ion-exchange 113, 272 -, liquid adsorption 55

-, paper 14, 52, 113, 114, 116, 205 -, partition 52, 113, 272 -, thin layer 53 -, vapor phase 233 Chromogenic substrates 235 Chymotrypsin 57, 117, 157 Cinnamaldehyde 219 Claviceps purpurea 193 Co-ill complexes 239 CoenzymeA 269 Complexones 21, 203 -, macrocyclic 214 Condensation, four-center (4CC) 99,233 -, oxidation/reduction 98 D-Configuration 186 Conformation, peptide 245 Copolymers, styrene/divinylbenzene 104 Corticotropin 103, 163ff, 230, 236, 241,

266 Cotton effect 121, 122 Countercurrent distribution 55, 137, 143,

265 - -, vasopressin/oxytocin 155 - -, gramicidins 203 Coupling, active esters 87 -, BOP 92, 232 -, racemization-free 266 - reagents 77,93, 108 - -, ethoxyacetylene 88, 241 -, segments 242 -, side reactions 94ff Cryptands 203 Crystal structure analysis 132 p-Cyanoalanine 96, 109 Cyanobacterium 222 'Y-Cyanobutyrine 109 Cyanogen bromide 117, 162 -, peptide cleavage 266, 274 Cyanoginosin-LA 222 Cyanomethyl esters 84, 271 Cyclic peptides see Cyclopeptides Cyclization 207 -, acid chloride activation 203 -, linear peptides 205,206 -, via disulfide fonnation 243 Cyclodepsipeptides 195 -, enniatins 20 Cyclodimerization, gramicidin 271 Cyclohexaglycine 206 Cyclols 194f,234, 270 -, anhydro- 196 Cyclononapeptide 216 Cyclopeptides 13, 205-207, 216, 232, 234,

239, 241, 271

Cyclopeptides, cytoprotective 216 -, homodetic/heterodetic 271 Cyclosporin A 21Of,211 Cyclotriglycine 206 Cyclotripeptides 196 Cyclotriproline 207 Cyclotrisarcosine 207 Cysteic acid 138 Cysteine 62, 113 -, disulfide bonds 12 Cystine 5 -, reduction to cystein, Na in liquid

ammonia 154 Cytochrome C 243

DANS peptides 115 DANS amino acids 115 DCC (dicyclohexylcarbodiimide), coupling

87-89, 91, 93, 94, 97, 108 Deacetylation, enzymatic 26 Deblocking, HCI in acetic acid 107 -, trifluoroacetic acid in dichloromethane

107 Decapeptide, cyclic, antamanide 212 Degradation, Edman 119, 120, 139, 167 -,non~atic 270 -, stepwise peptide 117,266 Dehydro-amino acid 44 Deletion peptides 110 Delicious peptide 189 Delta-sleep-inducing peptide 188, 247 Deprotection, final 108 -, hydrogen fluoride 271 Deprotonation 94 Depsipeptides 202,203,209,247 -, cyclo- 195,224 -, ionophoric cyclic 207 Derivatization, amino acids 113 Dermorphins 186, 266 Destroying angel 217, 220 Detoxification 17 Dextran, crosslinked (Sephadex) 55, 241 Di-benzyloxycarbonyl-L-cystine 142 Di-p-methoxytritylchloride 68 Diabetes insipidus 150, 157 Diabetes mellitus 157, 171 N-N' -Diacetyldiketopiperazine 45, 46 Diacylamine formation 46 Diacylation 241 Diastereoisomers 104 -,~tion 233 -, separation 239 Diastereomers 55

Subject Index 289

Diazo-fatty acid esters 27 Dicarba analog, oxytocin 147 Dicarbobenzoxy-L-cystine 64 Dicarbobenzoxylysine methyl ester 47 2,6-Dichlorobenzyloxycarbonyl group 67 Dicyclohexylcarbodiimide (DCC,DCCI)

87-94,97, 108 Diethyl chloroarsenite 92 Dihydroflavin adenine dinucleotide (F ADH)

16 Diisopropylcarbodiimide 108 Diketopiperazines 3,3,25,44,45, 110,

194, 195, 232 -, N-acetyl- 195 -, conformation 240 -, N-N' -diacetyl 45, 46 4,4' -Dimethoxybenzhydryloxycarbonyl

group 67 3,5-Dimethoxybenzyloxycarbonyl group 68 a,a-Dimethyl-3,5-dimethoxybenzyloxy­

carbonyl group (Ddz) 67 5-Dimethylamino-naphthalene-1-sulfonic

acid chloride (DANSyl chloride) 116 Dimethylformamide 82 2,4-Dinitrochloro~e 114 2,4-Dinitrofluorobenzene 115, 138, 271 2,4-Dinitrophenyl amino acids 115 2,4-Dinitrophenyl esters 87 Dinitrophenylation 138, 140 Dipeptidase 17 2,2' -Dipyridyl disulfide 98 Displacement analysis 49 Disulfide bond,reaction 65 - bridges 14,72,73 - chemistry 229 - formation from tritylthiols 170 - reduction, sodium in liquid ammonia 141,

143 1,4-Dithioerythrol (Cleland's reagent) 72 DNA 99,112,162,208 -, recombinant technology 113,117,162 DNP amino acids 115, 115 - peptides 115 Dowex 50 Dynorphin 187

Edman degradation 119, 139, 167 - -, gas-phase 120 EEDQ 91,94 Electron bombardment 129 Electrophoresis 4, 53, 273 Eledoisin 184f Eledon aldrOllandi 185

290 Subject Index

Eledon moschata 185 ~-Elimination 69, 70, 96 Elution analysis 49 Enantiomers 54 Endorphines 187, 268 Enkephalins 60, 187 -, analogs 188 -, cyclic derivatives 188 Enniatins 247 -, cyc10depsipeptides 20f Enzymatic synthesis 229 Enzymes, affinity binding 57 -, coupling with 99 Enzymology 68 Epidennal growth factor 188 Epidermin 223 Ergobasine 194 Ergot 3, 193f - alkaloids 3, 193f, 265 Ergotamine 193f -, thio- 198 Ergotinine 193 Ergotismus gangraenosus 193 Ergotoxin 193 Escherichia coli, insulin 162 ESR (electron spin resonance) 120, 127f Ester chlorides, reactive 229 Ester method 27 Esters, active 84ff, 108, 110, 111, 145,

161,167,206,235,240,241,243,264 -, -, catalysis 243 -, -, catalysis, aminolysis 240 -, -, coupling 87 -, -, insoluble 87 -, -, polymer-bound 111 -, -, water-soluble 237 Ethanolamide 209 Ethoxyacetylene coupling reagent 88, 241 Ethoxycarbonyl group 46 N-Ethoxycarbonyl group 69 Ethoxycarbonyl-2-ethoxy-l,2-dihydroquino-

line (EEDQ) 91 N-Ethoxycarbonylphthalimide 70 Ethylcarbonic acid mixed anhydride 91 Ethyl chlorocarbonate 81, 91 N-Ethylpiperidine 80 Exopeptidase 60

FADH 16 Fast atom bombardment (FAR) 130 Fast death factor 222 Fatty acids, gas chromatography 54 Fibrin 1,4

Ficin 60 Field desorption technique (FD) 130 Fischer projection 10 Flavianate 144 -, crystalline 141 Flavianic acid (2,4-dinitro-l-naphthol-7-

sulfonic acid) 48, 137 Fluorenyl methyloxycarbonyl group (Fmoc)

70, 71, 97, 107 Fluorescamine 51 Fmoc group 70, 71, 97, 107 Fonnate dehydrogenase 10 Fonnylmethionine 208 Four-center condensation (4CC) 99,233 Fourier transfonn 132 Fraction collector, automatic 52 Fragmentation of proteins 181 Freundlich-adsorption coefficients 49 Friedel-Crafts reactions 107 Frontal analysis 49 Fungisporin 207 Fusarium 20

~-Galactosidase 162 Galanin 169f GaleriTUl marginata 221 Gallbladder contracting honnone (chole-

cystokinin) 165f, 168, 188, 238 Gas chromatography 113, 273 Gastric inhibitory polypeptide (GIP) 168 Gastric juice, releasing honnones (factors)

172 Gastrin 136, 165f, 188, 244 -, little ("roinigastrin") 165 -, pyroglutamic acid 165 Gastrin II, tyrosin 165 Gelatine 28 Gila monster 187 Glucagon 167, 168, 171,233 -, synthesis 168 Glucose-dependent insulinotropic poly­

peptide (GIP) 168 Glumitocin (4-serine-8-glutamine oxytocin)

149 Glutamic acid 6, 48, 53, 66, 114 - -, poly-y-D- 236 D-Glutamic acid 236 Z-L-Glutamic acid a-methyl ester y-

chloride 65 Glutamine 62, 109, 142 -, introducing 228 y-Glutamyl transpeptidase 17 Glutathione 15f, 15

Glutathione synthesis 64,65 Glutathione-S-transferases 16 Glutathione peroxidase 10 Glycine 5,38,45, 114,238 Glycine ethyl ester 38 Glycopeptides 67,233 Glycosylation 9, 113 N-Glycylglycineanhydride 196 Glycylglycine, X-ray crystallography 132 Glyoxalase 17 - reaction 17 Graft polymers 111 Gramicidins 103, 114, 203f, 204, 208, 209,

239,244 -, antiparallel p-sheet 209 -, biosynthesis 208 -, cyclodimerization 271 Growth hormone (somatostatin) 170f,229,

242, 268 Growth hormone releasing hormone 172,

189 Guanidine derivatives 238 Gut peptides 189

a-Halogen fatty acids 29 Handle method 244 Heavy-metal ions 72 a-Helix 270 -, X-ray crystallography 132 Helodermin 187 Helospectin 187 Hemoglobin 5 -, X-ray crystallography 132 Hepatotoxic peptides 222 Heterodetic cyc10peptides 271 - peptides 13 Hexaglycine 30,31 Hexamethylsilazane 69 Hexapeptide, cyclic, NMR spectrum 126 Hippopotamus, lysine-vasopressin 150 Hippuric acid 25, 57 Hippmyl peptides 26 Histidine 6, 48, 49, 61, 62 Homodetic cyc10peptides 271 - peptides 13, 202 Hormone receptors,afflnity labeling 241 Hormones, gastrointestinal 186, 232, 233,

241,268,269 -, -, insulin-releasing effect 172 Hormones,peptide 136,232,243,267-269 -, -, antagonists 244 HPLC 54,61, 110, 169, 170 Hydantoin 29

Subject Index 291

Hydrazine 26, 116 Hydrazinoacids 234 Hydrazinolysis 116,238 Hydrides, complex 117 Hydrobromic acid 64 Hydrogenation, catalytic 47, 66 -, pa.Iladium/platinum catalyst 63 -, transfer 236 Hydrogen bonds, transannular, antamanide

215 Hydrogen fluoride,liquid 71, 107,238,

271 Hydrogen iodide 65 Hydroiodic acid 46 Hydrolysis,alkaline 105 -, amino acids 113 -, - -, partial 113, 114 -, enzymatic 56 Hydrophobic interactions, side chains 12 Hydroxamic acids 86 2-Hydroximinocyanoacetic acid 97 3-Hydroxy-3,4-dihydrobenzolriazine-4-one

94,98,109 3-Hydroxy-3,4-dihydroquinazoline-4-one

94,110 a-Hydroxyacyl1actames 194 I-Hydroxybenzolriazole esters 92-94 I-Hydroxybenzolriazole (HOBt) 86,87,93,

97,110,169 a-Hydroxyisovaleric acid 201 Hydroxylamine derivatives 86 N-Hydroxyphthalimides 85, 86, 243 Hydroxyproline 5, 6, 35 4-Hydroxyquinazoline-3-oxide 87 N-Hydroxysuccinimide 86,97 Hypertensin see Angiotensin Hypertension, angiotensin 182, 183 Hypothalamus 171

Imidazoles 196 -, acylation 87 Immunopeptides 189 Immunosuppression, cyclosporins 211 Indole, tryptophan 95 Infrared absorption 122f Inhibin 189 Insulin 44,72,73,77, 116, 138, 139, 147,

157ff, 228-231, 233, 234, 243, 244, 266-268,273,274

-, AlB chains 160 -, amino acid sequence (bovine/ovine/por-

cine/human) 159 -, analogs 161, 234 -, dinitrophenylation 158

292 Subject Index

InsuIin, disulfide bridges 158 -, human 161, 162 -, intennolecular interactions 160 -,ovine 161 -, oxidation with performic acid 158 -, oxidative sulfitolysis 160 -, porcine 60 -, -, desalanino 162 -, proteolytic enzymes 159 -, recombination experiments 160 -, releasing effect, gastrointestinal honnones

172 -, retrosynthetic analysis 161 -, sequence determination 2 -, structure 158f -, structure-3D 157, 159 ", synthesis 160f -, Zn complex 158 -, Zn, X-ray crystallography 132, 133 Ion-exchange chromatography 49,55 Ion-exchange resins 111 Ion conductance 209,210 Ionization, chemical 129 Ionophores 21, 203, 214 -, artificial 203 Ion transport, membrane 230 - -, valinomycin 201 Isobutylcarbonic acid mixed anhydrides 81 a-Isocyanatocarbonic acids 36 Isoenzymes 273 Isoleucine 7, 81, 142 -, y,a-dihydroxy- 221 -, NMR 125 N-Isopenicillin 198-200 Isopropyl chlorocarbonate 81 Isotocin (4-serine-8-isoleucine oxytocin)

148 Isotope dilution method 114 Isovaleric acid acylamino acid mixed anhy-

drides 82 Isovaleryl chloride 82 Isoxazole ring 90 Isoxazolium salts 90

Kallidin 183f -, methionyl- 183 Kassinin 185 Keteneimines 90

Lactam/lactone rings 13 y-Lactone 117 Lactones, macrocyclic, insertion reaction

194, 195

Langerhans islet cells 157 Lanthionine 113,222,223,223,234,235,

238 Lantibiotics 222f, 234 Lepiota mushrooms 221 Leuchs' substances 268 Leucine 2, 5, 35 - anilide 57 -, L-y,&-dihydroxy- 217 -, y-hydroxy- 218, 219 -, NMR 125 Leucokinins 189 L-Leucylnonaglycine 31 Leukotrienes 17 LH-RH see Luteinizing honnone releasing

honnone LiAlH4 128 Liquid phase methods 234, 238 Litorea aurea 186 Litorea (Hyla) caerulea 166 Litorin 186 LSD 194 Luteinizing honnone releasing honnone

(LH-RH) 172 - - - -, analogs 239 Lycomarasmin 19f Lysergic acid 194 Lysine 6, 48, 49, 61 Lysine-vasopressin 85

Macrocyclic lactones, formed by insertion 194, 195

Macromolecules, soluble 247 -, X-ray crystallography 132 Magainins 189 Malformin 19f Mass spectrometry (MS) 113, 119, 120,

128f, 213, 232, 273 - -, derivatization 128 - -, fragmentation 130 Mastoparan 187 Melanocyte stimulating hormones (a-/~­

MSH) 163, 164 Mellitin 186 3-Mercapto-3,3-pentamethylene propionic

acid 148 ~-Mercaptoethanesulfonic acid 229 Merrifield resin 105 Mesotocin (8-isoleucine oxytocin) 148 Met-enkephalin 60 Metal ions, antamanide 215, 216 Methanolysis 129 Methionine 7,95, 117

p-Methoxybenzyloxycarbonyl group 107 2-D-Methyl-3-mercaptopropionyl-L-proline

183 N-Methyl-acetamide 123 I-Methyl-histidine 15 N-Methyl-peptides 129 N-Methylamino acids 96 Methyl esters 84 - -, aminolysis 84 - -, ammonolysis 84 4-(Methylsulfonyl)-phenylsulfonylethyl­

oxycarbonyl (Mpc) group 243 Methy1sulfonylethyloxycarbonyl group

(Msc) 243 Microbiological assays 114 Microcystins 222f Microcystis aeruginosa 222 Molecular conformations, NOE effect 125 Morphine receptor 187 Morphine-modulating peptide 189 Morpholine 70 Motilin 168f MS see Mass spectrometry MSH 103, 163, 164 Myoglobin 5 -, X-ray chrystallography 132

Nactins 203 Natriuretic factors 189 NCAs (N-Carboxyanhydrides) 35f, 37,41 -, polymerization 38, 39 Neurohypophysis 137, 149, 157 -, hormones 231,242,244 Neuromedins 189 Neuropeptides 168,239 -, VIP 168 Neurophysin complex 127, 148 Neurotoxic alkaloids 222 Neurotransmitters 267 Newsprint reaction 220 Ninhydrin 51, 52, 113 Nisin 222, 223, 267 2-Nitro-4,5-dirnethoxy-Z 68 p-Nitrophenyl esters 85,108, 109, 196,205 o-N!trophenylsulfenyl group 68, 235 p-Nltrothiophenyl esters 85, 244 NMR 113, 120, 125f, 214, 229 -, 2D 127, 234, 242 -, oxytocin 148 NOE effect, molecular confonnations 125 Nomenclature/symbols 10, 11 Nonapeptides, blocked 143, 145 Nuclear Overhauser enhancement (NOE

effect) 125

Subject Index 293

Nucleic acids 224 see also DNA and RNA

- -, sequencing 113 Nucleophile, auxiliary 93, 94 Nucleotides 53

Oc~tide 30,31,35 Ophthalmic acid 15, 18f Opioid peptides 60, 187f, 230, 237, 266 ORD (optical rotatory dispersion) 120, 121 Ornithine 205,235 Orthogonal combination 108 Osteoporosis 170 Ovalbumin 2,4 Oxazolidine-2,4-diones 36 5(4H)-Oxazolones 96 Oxytocin 77, 82, 83, 85, 1m, 127, 136,

137ff, 154, 157, 167,188,231,232,236, 242,243,246

-, 4-serine-8-glutamine (glumitocin) 149 -, 4-serine-8-isoleucine (isotocin) 148 -,4-threonine-7-glycine 148 -, 8-isoleucine (mesotocin) 148 -, analogs 146, 148:155 -, antagonist 148 -, antiarrhythmic action 149 -, carba analogs 147, 156 -, carboxamide groups 148 -, child birth 149 -, chromatography 137 -, confonnation 147, 148 -, cyclic structure 146 -, desamino 146-148, 155 -, desamino-hydroxy 148 -, dicarba analogs 147, 156 -, dimers 147 -, disulfide bridge 146 -, electropherograms 140 -, electrophoresis 137 -, glycyl- 148 -, honnonal activity 141 -, killfish spawning reflex 149 -, lifespan of male rats 149 -, NMR 148 -, partial acid hydrolysis 140 -, partition chromatography 155 -, receptors 146, 148, 156 -, synthesis 140f Oxytryptophan 217

Pancreozymin 166 Papain 56,57,60 Parathyroid honnone (PTH) 169f, 238

294 Subject Index

Parathyroid hormone, human (PTHh) 169 - -, pre- 169 Partition coefficient 52 Penicillamine 148, 154 Penicillanic acid, 6-amino- 198, 200 Penicillin 123, 137, 154, 198f, 199, 199,

201, 243, 267, 271 -, benzyl- 154 -, biosynthesis 199 -, IR analysis 123 - ,iso- 198, 199 -, peptidoglycan inhibition 201 -, semisynthesis 241 -, thiazolidine-/3-1actam 198, 199 Penicillinase 154, 198 Pentafluorophenol 109 Pentafluorophenyl esters 85, 87 Pepsin 56 Peptidases 56 'Y-Peptide 15 Peptide bonds, cis/trans 11,12 - -, trans, X-ray crystallography 132 Peptide formation, enzymatic 59 Peptide synthesizer, automatic 68 Peptide-lipid interactions 230 Peptides, biosynthesis 269 -, channel-forming 267 -, cyclic 13, 205-207, 232, 239, 241 -, cyclic microbial 208 -, cysteine 270 -, dehydro- 246 -, gastrointestinal 236 -, hepatotoxic 222 -, membrane-active 270 -, sulfur-containing 246 -, venom 186f Peptidolipids 232 Peptones 2 Performic acid 144 Periodicity rule 4 Permethylation 129 Permutites 49 Phalloidin 211, 214, 216, 217 Phalloin 217 -, synthesis 218, 219 Phallotoxins 212, 216, 217, 221 -, F-actin filament stabilization 218 Phenols 87 Phenylthiohydantoins (PTHs) 119,119 S-Phenyl-N-acetyl-L-cysteine 16 Phenyl-propyl-2-oxycarbonyl group 66 Phenylalanine 6,49, '20, 145 -, NMR 125 -, UV 121

Phenylalanine anilide 37 Phenylalaninol 210 Phenylalanyl-phenylalanine anilide 37 N-Phenylcarbamoyl peptides 118 Phenyl esters 85 - -, ammonolysis 85 Phenylglycine, racemization 96 Phenylhydantoin 117, 118 -, stepwise degradation 118 Phenylhydrazines 23 Phenylisocyanate 117 Phenylisopropyloxycarbonyl group 107 Phenylisothiocyanate 118 Phenylmercapturic acid 16 PHM-27 168 Phosphonium iodide 46, 65 Phosphopantetheine 208 Phosphoric acid mixed anhydride 92 Phosphorous acid, diesters 82 Phosphoserine 240 Phosphotungstic acid 48 Photolysis 68f Phthaloyl group 202 Phthalyl group 69,70 Phyllomedusa bieolor 185 Phyllomedusa rhodei 186 Phyllomedusin 185 Physalaemin 185 Physalaemus fuscumaculatus 185 Phytotoxins 19 Piperidine 70 Pituitary gland 137, 149, 163 - hormones 154, 155 Plastein 57 - reaction 59 Pleated J3-sheet, X-ray crystallography 132 Poly-L-Iysine, CD spectra 123 Polyacrylamide gels 4, 53 Poly alanine 40 Poly amino acids 37,38, 40f, 237, 268, 274 - -,IR 124 Polyamino alcohols 128 Polyaspartic acids 24 Polyethyleneglycol 234 Polyglutamic acids 40 Polyglycines 38, 40 - esters 38 Polylysines 40 Polymer-bound active esters 111 Polymeric supports 109, 110 - -, insoluble 85, 103, 145, 161, 240 Polymeric reagents 270 Polymers, soluble 111 Polymyxins 242

Polynucleotides 112 Polypeptides 113 -, definition 2 -, IR 124 Polyprolines 40 Popcorn resin 104 Posttranslational processing 186 - - modification 9, 113 - - -, glutamic acid 9 Pr~ohormones 181, 189 Presomatostatin 171 Pro-opiocortin 188 Prohormones 181, 189 Proinsulin 161, 162, 234 - to insulin 163 Proline 6, 96, 235 -, 2,3-trans-3,4-trans-3,4-dihydroxy-L-

218 -, 4-cis-hydroxy- 217 -, 4-trans-hydroxy- 221 N-Prolyl-cyclo-dialanine 196 Propen-1-yloxycarbonyl group 67 Protecting groups 62 - -, amino- 29 - -, carboxyl 70 - -, sulfhydryl 235 - -, urethane-type 97 N-Protecting groups 105 S-Protecting groups 72 Proteinases 56, 58 Protein cleavage, non-enzymatic 274 - crystals, X-ray crystallography 132 - fragmentation 181 -, protoplasmic 1 - synthesis 59 Proteolytic enzymes 56, 62, 99 Protonation 94 Protoplasmic proteins 1 PTH (parathyroid hormone) 169f Purification, amino acids 113 -, peptides 237 Purines 266 Pyrazole 87 Pyridinium chloride 240 Pyroglutamic acid, gastrin 165 Pyroglutamyl residue 228 - -, eledoisin 185 Pyrrolinones 52

Quinoline 91 Quinoxolines 224

Subject Index 295

Racemization 61, 81, 91, 93-96, 233, 244, 272

-, prevention through additives 234, 240 -, proton abstraction 89 -, suppressing additives 97 -, urethane-type blocking groups 65 Radicals 127 Radioimmunoassay 220 Raleigh scattering 123 Ramachandran plot 12, 236 Raman spectra 122f Rana pipiens 186 Ranatensin 186 Raney nickel 139 Receptor-agonist interactions 242 Recombinant DNA technology 113, 117, 162 Reduction, electrolytic 26 Reinecke acid (tetrarhodanatodiaminchromic

acid) 48 Releasing factors (releasing hormones) 17lf, 246, 266 Releasing hormones (releasing factors) 171f, 246,266 Renin 181, 182 -, inhibitors 182, 183, 246 Resins, "popcorn" 104 Resins, Merrifield 105 Resonance stabilization 11 Restriction enzymes, insulin production 162 Rhodanilic acid 48 Ribonuclease A 41, 237, 239, 243, 269, 272 -, structure elucidation 51 -, synthetic 170 -, IH-NMR spectrum 127 -, NMR 125 Ribosomes, protein synthesis 59,207 Rigin 189 RNA polymerase 221 RNA, messenger 113,208 -, transfer 59, 207 Rotation, specific 144 Ruhemann's purple 51

S-peptide 41,237,271 S-protein 41 Safety-catch 70 Salicylic acid 197 Saponification resistance, tert-butyl group

66

296 Subject Index

Sarcosine 206, 224 Sauvagine 186 Scorpion toxins 240 Secolactone 218 Secretin 85, 136, 167f, 231, 234, 241, 243,

246,265,269 -, biosynthesis in bacteria 167 -, condensation of segments 167 -, Edman degradation 167 -, glucagon homology 167 -, stepwise synthesis 167 -, trypsin fragmentation 167 Selenocysteine 10 Semisynthesis, protein 242 Sephadex 55,241 Sequenator, automatic 119, 120, 229 Sequence peak ions 129 Serine 6,61,62,67,238 -, phospho- 240 D-Serine 217 4-Serine-8-glutamine oxytocin 149 Serratamolide 195,196 p-Sheet, antiparallel, gramicidin 209 Silico-organic compounds 68f Silk fibroin, X-rays 3 Silver glycinate 79 Silybum marianum 220 Silyl esters 69 N-Silyl group 69 S-Silyl compounds 69 Silymarin 220 Simultaneous multiple peptide synthesis

(SMPS) 111 Sodium dodecylsulfate 4, 53 Solid-phase peptide synthesis 103ff, 234,

238,245,247 - - - -, automation 109 - - - -, Letsinger's approach 105 - - - -, Merrifield's approach 106, 108 Solubility product method 48, 114 Somatostatin 17Of, 229, 242, 268 -, bicyclic analog 171, 171 -, carba analogs 171 -, human 172 -, pre- 171 -, solid-phase synthesis 171 Spectroscopic methods 114, 120f Spin-spin coupling 125 Staphylococcus epidermidis 223 Stereoisomers, FIscher convention 23 Steroids, adrenal cortex 163 Strategy, stepwise 103 Strychnine alkaloids 36 Styrene/divinylbenzene copolymers 104

Substance P 184, 185, 232 Sulfhydryl protecting groups 146, 147,235 Sulfitolysis 72, 72 Syntheses, enzymatic 57,59

Tachikinins 186 Tea-bag method 111 Tetraethyl pyrophosphate 92 - pyrophosphite 82, 143 Tetraglycine ethylester 27, 38 2,2,5,5-Tetramethylpyrrolidine-l-oxide 127 Tetrapeptides, cyclic 207 Tetrazole 87 TFA-amino acid 70 - - esters 54 TFA-peptides 70 Theobromine 232 Thermolysin 60 Thiazolidine-p-Iactam 154 -, penicillin G 198, 199 Thiazolidine-azlactone structure 154 N-Thiocarbamic acid anhydrides (TeAs)

41 Thioergotamine .198 Thioester crosslinks 217 Thioether amino acids 223 - bridge 218 Thiol esters 208 - function 230 Thioltransferases 15 Thiolysis 72 Thionyl chloride 29 Thiophenol 84, 87 Thiophenyl esters 78 - -, aminolysis 85 Thiorhodanides 72 Thiostrepton 244 Thiotemplate mechanism 208, 211, 223 Thioureido compounds 118 Threonine 7, 61, 62, 67, 238 -, tert-butyl ester 162 D-Threonine 217 Thrombin inhibitors 236 Thyrocalcitonin 170 Thyroid hormones 169f Thyroliberin (TRHII'RF) 172 Thyrotropin releasing hormone (fRH/fRF/

thyroliberin) 172 Toadstools see Amanita N-p-Toluenesulfonyl group 107 Toluenesulfonyl residue 64 p-Toluenesulfonyl-L-glutamic acid 142 p-Toluenesulfonyl-L-pyroglutamyl-L-asp-

aragine 142

2-(4-Toluenesulfonylmethyl)ethoxycarbonyl group 70

p-Toluenesulfonyl-pyroglutamic acid 142 Tolypocladium injlatum 211 Tosylamino acid chlorides 229 Transesterification 230, 240 -, base-induced 88 Transpeptidation 60 TRH see Thyrotropin releasing hormone Tri-p-methoxytritylchloride 68 1,2,4-Triazole 87 Trichloroacetic acid 68 2,4,5-Trichlorophenyl esters 85, 109 Trichoderma viride 210 TricluJderma polys porum 211 Triethyl phosphate 247 - phosphite 247 Trifluoroacetic acid 54, 64, 67, 70, 107,

108, 110, 119, 164, 233 Trifluoroacetyl-L-dipeptide cyclohexyl

esters 55 Trifluoroacetylation 54 N-Trifluoroacetyl derivatives 273 Trifluoroacetylpeptide esters 129 - methyl esters 129 Trifluoromethanesulfonic acid 107 Triglycine, IR spectrum 124 Triglycine azide 206 Trimethylchlorosilane 69 Trimethylfluorosilane 69 Trimethylsilyl group 69 Trimethylsilylethyl esters 69 Triphenylmethyl group 67, 71, 205 Triphenylphosphine 98 Trityl group 68, 232 N-Trityl compounds 68 S-Trityl-cysteine 71 Truncated sequences 110 Trypanothione 18 Trypsin 56,57,59, 117, 151, 157, 162,

167, 182, 183 Tryptathionine 217 Tryptophan 6, 49, 120 -, indole 95 -, NMR 125 -, UV 121 Tryptophan synthetase 162 Tryptophillin 186 Tuftsin 189 Tyrocidines 203,204,207 Tyrosine 2, 5, 49, 61, 62, 120, 145 -, NMR 125 -, UV 121 Tyrothricin 203, 207

Ultracentrifuge 4 Uperolein 185 Urethane 81

Subject Index 297

Urethane-type blocking groups 65 Urogastrone 188 UV spectroscopy 120f

Vaccines, synthetic 189 Valine 6,81 -, NMR 125 Valinomycin 20lf, 201, 247 Valinomycin-K+ complex 201, 202, 214 van Dyke protein 148 Vasoactive intestinal peptide (VIP) 168,

189,243 Vasopressin 136, 149ff, 154, 157, 188 -, agonists 151 -, amino acid sequence 155 -, analogs 150, 151,241 -, antidiuretic effect 149, 151 -, arginine- 149, 150, 152 -, arginine-,ureido group 150 -, chromatography 137 -, citrullin analog 150 -, 1-desamino-8-D-arginine 150 -, diabetes insipidus 150 -, Edman degradation 155 -, effect on memory 152 -, electrophoresis 137 -, 8-homolysine 150 -, 8-homonorleucine 150 -, 8-E-hydroxynorleucine 150 -, inhibitors 151 -, lysine- 85, 147, 149, 150 -, 2-(I-mercaptocyclohexyl) acetic acid 151 -, 8-ornithine 150 -, receptors 148 -, -, electrostatic interactions 150 Vasotocin 152 -, arginine- 152 -, lysine- 15 Venom peptides 186f Vespulakinin 187 Vibrational spectroscopy 122f Vinyl esters, ammonolysis 85 VIP 168, 189, 243 Virotoxins 217 Vitamin B'2 267

Walden inversion 29 Woodward's Reagent K 90

298 Subject Index

X-ray diffraction analysis 4, 131ff, 214, 215,221,267,268

- -, D-isoleucine 10 - -, single crystals 125 - -, valinomycin 202

X-rays, silk fibroin 3

Z-chloride 63 Zn-insulin 158, 160 -, X-ray crystallography 132

M.Bodanszky, Case Western Reserve University, Cleveland,OH

Principles of Peptide Synthesis 1984. XVI, 307 pp. (Reactivity and Structure, Vol. 16) Hardcover DM 160,- ISBN 3-540-12395-4

Contents: Introduction. - Activation and Coupling. - Reversible Blocking of Amino and Carboxyl Groups. - Semipermanent Protection of Side Chain Functions. - Side Reactions in Peptide Synthesis. - Tactics and Strategy in Peptide Synthesis. - Tech­niques for the Facilitation of Peptide Synthesis. - Recent Developments and Perspectives. - Author Index. - Subject Index.

M.Bodanszky, A.Bodanszky, Case Western Reserve University, Cleveland,OH

The Practice of Peptide Synthesis 1984. XVII, 284 pp. (Reactivity and Structure, Vol. 21) Hardcover DM 168,- ISBN 3-540-13471-9

Contents: Introduction. - Protecting Groups. - Activation and Coupling. -Removal of Protecting Groups. - Special Procedures. - Models for the Study of Racemization. - Reagents for Peptide Synthesis. - Appendix. - Author Index. - Subject Index.

A textbook resulting from years of experience

M. Bodanszky, Princeton, NJ

Peptide Chemistry A Practical Textbook

1988. XII, 200 pp. 2 figs. 5 tabs. Softcover DM 48,­ISBN 3-540-18984-X

Contents: Introduction. - Structure Determination: Amino Acid Analysis. Sequence Determination. Secondary and Tertiary Structure. - Peptide Synthesis: Formation of the Peptide Bond. Protection of Functional Groups. Undesired Reactions during Synthesis. Racemization. Design of Schemes for Peptide Synthesis. Solid Phase Peptide Synthesis. - Methods of Facilitation. Analysis and Characterization of Synthetic Peptides. -Subject Index.

T. Wieland, Heidelberg

Peptides of Poisonous Amanita Mushrooms 1986. XIV, 256 pp. 78 figs. (Springer Series in Molecular Biology) Hardcover DM 198,- ISBN 3-540-16641-6

Contents: Introduction. - Mushrooms Causing Death in Rare Cases. -Deadly Poisonous Amanita Mushrooms and Their Constituents. - Toadstools Accumulating Amatoxins. - Poisoning by Amatoxins. - Two Centuries of Amanita Research. - Recognition, Isolation and Characterization of the Peptide Toxins. - The Chemistry of the Amatoxins, Phallotoxins and Virotoxins. - Molecular Pathology ofthe Amanita Peptides. -Non-Toxic Peptides from Amanita phalloides. -Phallolysin. - Retrospectives and Outlook. -References. - Subject Index.