PeptidesChemistry and Biology

Proceedings of the Tenth American Peptide Symposium

May 23-28, 1987, St. Louis, Missouri, U.S.A.

Edited by

Garland R. Marshall

Department of Pharmacology

Washington University School of Medicine

St. Louis, Missouri 63110, U.S.A.

UN1VLIIC1T/TRP!HUOTHEKh.Ai 'i'1Jv'LR

Ti:f>'ri;ocHr:

INFORM/0VOr!Sb;EU.IQTHEK

ESCOM Leiden 1988

Contents

Preface v

Tenth American Peptide Symposium Committees viii

Sponsors, Donors and Contributors ix

Abbreviations x

Sixth Alan E. Pierce Award Lecture

Naturally occurring active peptides from anterior pituitary and gonads 3

C.H.Li

Session I: Conformation of peptides

Circular dichroism measurement of peptide helix unfolding 15

K.R. Shoemaker, R. Fairman, E.J. York, J.M. Stewart andR.L. Baldwin

Theoretical studies of protein structure 21

F.E. Cohen and I.D. Kuntz

Solution structures of defensins: Naturally occurring peptide antibiotics 27

A.C. Bach II, X.-L. Zhang, D.R. Hare and A. Pardi

Action of alanine-rich antifreeze polypeptides: Dipole moment of a- 32

helix for ice recognitionA. Chakrabartty, C.L. Hew, D. Yang and M. Sax

Conformational analysis of a cyclic hexapeptide by rotating frame NOE 35

(ROE) evaluation and molecular dynamics (MD) calculations

H. Kessler, K. Wagner and M. Will

13C NMR T, studies and enantiotopomerisations of 3l0-helical poly- 37

peptidesG. Jung, R.-P. Hummel, K.-P. Voges, K. Albert and C. Toniolo

xv

Contents

The conformation of oxytocin bound to neurophysin I 39

K. Hallenga, N.R. Nirmala, D.D. Smith and V.J. Hruby

Conformational analysis of human atrial natriuretic polypeptide by 42

NMR and distance geometry algorithmY. Kobayashi, T. Ohkubo, Y. Kyogoku, S. Koyama, M. Kobayashiand N. Go

The structure of a new hexameric form of human insulin 44

G.D. Smith, D.C. Swenson, Z. Derewenda, E.J. Dodson, G.G. Dodson,CD. Reynolds and K. Sparks

Comparative 2D NMR studies of the Phe B24 -* Leu mutant human 47

insulin

M.A. Weiss, E. O'Shea, K. Inouye, B.H. Frank, I. Khait, D. Nguyen,L.J. Neuringer and S.E. Shoelson

Hexapeptide metal binding domains in proteins 51

H.A. Anderson, M.A. Eastman, L.G. Pedersen, R.G. Hiskey and A.T.

Hagler

Conformation of the flap of human renin 54

J.A. Fehrentz, A. Heitz, F. Heitz, C. Carelli, F.X. Galen, P. Corvol

andB. Castro

Isotope-filtered proton NMR experiments for the conformational de- 57

termination of peptides in solution and bound to biomacromolecules

S.W. Fesik, R.T. Gampe, Jr., E.T. Olejniczak, J.R. Luly, H.H. Stein

and T. W. Rockway

Modulation of membrane morphology by basic proteins and polypep- 60

tides

P.E. Fraser and CM. Deber

An application of distance geometry in the modeling of peptides: A 62

molecular complex of the aglycon of aridicin A

J.C. Hempel, L. Mueller, S.L. Heald and P.W. Jeffs

Vibrational circular dichroism of polyproline 65

R. Kobrinskaya, S. C. Yasui and T.A. Keiderling

Conformational mobility in the vasopressin series 68

C.W. DeBrosse, J.C. Hempel and K.D. Kopple

xvi

Contents

Conformation and motion of biologically active peptides as bound to 71

phospholipid membraneA. Milon, K. Wakamatsu, K. Saito, A. Okada, T. Miyazawa and T.

Higashijima

Two-dimensional NMR and computer modeling studies of two con- 74

formers of an actinomycin-related peptide lactone

A.B. Mauger, J.A. Ferretti, K.S. Gallagher andJ.V. Silverton

2D NMR evaluation of 3D structure of scorpion Buthus eupeus neu- 77

rotoxin M, in solution

V.S. Pashkov, N. A. Hoang, V.N. Maiorov and V.F. Bystrov

'H NMR and CD studies of tfes-Trp1, Nle12-rninigastrin in H20/TFE 79

N.J. Mammi, S. Mammi and E. Peggion

Conformational analysis of 5,5-dimethylthiazolidine-4-carboxylic acid 81

(Dtc), a readily available proline analog/. Samanen, T. Cash, D.S. Eggleston andM. Saunders

Conformational analysis of model cyclic endothiopeptides by NMR and 84

molecular modeling techniquesD.B. Sherman, R.A. Porter and A.F. Spatola

Peptide inhibitor binding to bacterial collagenase by proton NMR 87

relaxation studies: A direct approach to structure-activity relationshipsF. Toma, V. Dive andA. Yiotakis

Vibrational circular dichroism of aromatic polypeptides 90

S. C. Yasui and T.A. Keiderling

Crystal and molecular structure of S-deoxo [y(R) hydroxy-Ile3]-amanin: 93

amide: A synthetic analog of Amanita toxins

G. Zanotti, T. Wieland, E. Benedetti, B. Di Blasio, V. Pavone and C.

Redone

Session II: Peptide mimetics

Design and comparison of nonpeptide and peptide CCK antagonists 97

R.M. Freidinger, P.S. Anderson, M.G. Bock, R.S.L. Chang, R.M.

DiPardo, B.E. Evans, V.M. Garsky, V.J. Lotii, K.E. Rittle, D.F. Veber

and W.L. Whitter

xvn

Contents

On the importance of the peptide bonds in the C-terminal tetrapeptide 101

of gastrin and in the C-terminal heptapeptide of cholecystokininM. Rodriguez, P. Fulcrand, M.-F. Lignon, M.-C. Galas, J.-P. Bali, R.

Magous, P. Dubreuil, J. Law and J. Martinez

Reverse turn mimics 105

W.F. Huffman, J.F. Callahan, D.S. Eggleston, K.A. Newlander, D.T.

Takata, E.E. Codd, R.F. Walker, P.W. Schiller, C. Lemieux, W.S.

Wire and T.F. Burks

Nonpeptide mimetics ofjaspamide 109

M. Kahn and T. Su

trans Carbon-carbon double bond isosteres of the peptide bond: General 112

methodology and the synthesis of cholecystokinin (CCK) analogsY.K. Shue, G.M. Carrera, Jr., A.M. Nadzan, J.F. Kerwin, H. Kopeckaand C. W. Lin

Conformations of cholecystokinin and their relationships to rigid 115

molecules

R.A. Hughes and P.R. Andrews

Acyl lysinamido phosphonates: Potent, long-acting inhibitors of an- 118

giotensin-converting enzyme

M.J. Loots, M.C. Badia, D.W. Cushman, J.M. DeForrest, D.S. Ka-

ranewsky, M.G. Petri, E.W. Petrillo, Jr. and J.R. Powell

Diaminoalcohols and diaminoketones: Potent inhibitors of an enke- 120

phalin-degrading rat brain aminopeptidaseN.G. Delaney, E.M. Gordon, M.M. Asaad, D. W. Cushman, D.E. Ryono,R. Neubeck and S. Natarajan

Synthesis of conformational^ constrained CCK-4 analogs containing 123

a substituted gamma lactam ringD.S. Garvey, P.D. May and A.M. Nadzan

A dehydro-keto-methylene inhibitor of substance P degradation 126

A. Ewenson, R. Laufer, J. Frey, E. Rosenkovich, M. Chorev, Z. Selingerand C. Gilon

Synthesis and properties of some peptides related to the bicyclic 8- 129

turn dipeptide (BTD)U. Nagai, R. Kato, K. Sato, N. Ling, T. Matsuzaki and Y. Tomotake

Tripeptide aminoalcohols: A new class of human renin inhibitors 131

S. Natarajan, C.A. Free, E.F. Sabo, J. Lin, E.R. Spitzmiller, S.G.

Samaniego, S.A. Smith andL.M. Zanoni

xvui

Contents

Synthesis and antagonist activities of backbone-modified angiotensin 134

II analogsW.H. Roark, F.J. Tinney and E.D. Nicolaides

A position seven analog of angiotensin II with potent antagonist activity 137

J. Samanen, J. C. Hempel, D. Narindray and D. Regoli

Session III: Analytic and synthetic methods

Asymmetric synthesis of amino acids 143

D.A. Evans, A.E. Weber, T.C. Britton, J.A. Ellman and E.B. Sjogren

Asymmetric syntheses of /3-OH and /3-OH, 7-alkyl a-arnino acids: 149

Analogs of the unusual cyclosporin amino acid MeBmt

R.D. Tung, C.-Q. Sun, D. Deyo and D.H. Rich

Activation and racemization in peptide bond formation 152

N.L. Benoiton andF.M.F. Chen

Development of methodology for arginine and jv*-alpha protection in 157

peptide synthesisR. Ramage, J. Green and M.R. Florence

Solid phase synthesis ofC-terminal peptide amides under mild conditions 159

F. Albericio, N. Kneib-Cordonier, L. Gera, R.P. Hammer, D. Hudson

and G. Barany

Total synthesis of porcine and human cholecystokinin-33 (CCK-33) by 162

the classical solution procedureY. Kurano, T. Kimura and S. Sakakibara

Simultaneous multiple peptide synthesis: The rapid preparation of large 166

numbers of discrete peptides for biological, immunological, and meth¬

odological studies

R.A. Houghten, J.H. Cuervo, J.M. Ostresh, M.K. Bray and N.D. Frizzell

Synthesis and characterization of peptides and proteins 173

S.B.H. Kent, K.F. Parker, D.L. Schiller, D.D.-L. Woo, I. Clark-Lewis

andB.T. Chait

Chiral synthesis of D-a,w-diaminoalkanoic acids 179

P.L. Beaulieu and P. W. Schiller

Synthesis of anglerfish peptide YG (APY) 181

A. Balasubramaniam, D.F. Rigel, P. C. Andrews, J.E. Dixon, R.L. Jackson

andJ.E. Fischer

xix

Contents

A mild and novel approach to sulfation of serine- and threonine- 184

containing peptides during the SN2 deprotection step

R.H. Berg, A. Holm and J.P. Tarn

Synthesis of an e(7-Glu)Lys cross-linked peptide in human fibrin 187

M.S. Bernatowicz, C.E. Costello and G.R. Matsueda

Use of Fmoc amino acid chlorides in peptide synthesis 189

M. Beyermann, D. Granitza, M. Bienert, B. Mehlis, H. Niedrich and

L.A. Carpino

Studies of acetamidomethyl as cysteine protection: Application in 192

synthesis of ANF analogsS.F. Brady, W.J. Paleveda and R.F. Nutt

Analysis and enantiomeric resolution of a-alkyl-a-amino acids 195

H. Bruckner, I. Bosch, S. Ktihne and S. Zivny

Automated Fmoc synthesis on polystyrene resins 198

H. Beilan, D.L. Noble, C.P. Ashton and D.P. Hadfield

Chemical synthesis of human epidermal growth factor (EGF) and human 202

type a transforming growth factor (TGFa)R. DiMarchi, E. Osborne, E. Roberts and L. Slieker

Design, construction and application of an automated large scale solid 204

phase peptide synthesizer: Large scale preparation ofvasopressin analogsM.S. Edelstein, J.L. Hughes, P.K. Bhatnagar, J.E. Foster, K.D. Tubman,

S. Kalbag, A. Patel, P. Voelker, D. Narindray, A.R. Culwell and M.

Sherlund

Solid phase synthesis using high-titer resins 208

M.S. Edelstein, J.L. Hughes, J.E. Foster and A.R. Culwell

Rapid solid phase peptide synthesis on a controlled pore glass support 210

K. Buttner, H. Zahn and W.H. Fischer

Solid phase peptide synthesis using BOP reagent: Synthesis of growth 212

hormone releasing factor (GRF) analogsA. Fournier, C.-T. Wang and A.M. Felix

Continuous flow peptide synthesis 215

7?. Frank, H. Leban, M. Kraft and H. Gausepohl

Two new disulfide bonding reactions for the synthesis of cystine peptides 217

N. Fujii, A. Otaka, O. Ikemura, T. Watanabe, H. Aral, S. Funakoshi

and H. Yajima

xx

Contents

Kinetics of coupling reactions in solid phase peptide synthesis 220

B. Hetnarski and R.B. Merrifield

The utility of reductive alkylation in solid phase peptide synthesis 223

S.J. Hocart, N. Y. Jiang, M. V. Nekola and D.H. Coy

A novel approach to the purification of peptides by reversed-phaseHPLC: Sample displacement chromatography 226

R.S. Hodges, T.W.L. Burke and C.T. Mant

A deprotection method using tetrachlorosilane-trifluoroacetic acid sea- 229

vengers by a 'reductive acidolysis' mechanism: Application to the

synthesis of a novel tachykinin peptide, scyliorhinin I

Y. Kiso, M. Yoshida, T. Kimura, T. Mimoto, M. Shimokwa and T.

Fujisaki

Studies related to the syntheses of pseudobactin 232

T. Kolasa and M.J. Miller

Chlorotrimethylsilane-phenol as a selective deprotection reagent for the 236

zer/-butyloxycarbonyl group

E. Kaiser, Sr., P.M. Kubiak, J.P. Tarn and R.B. Merrifield

Synthesis of peptides containing a,a-disubstituted amino acids: Experi- 239

ments related to a,a-diethylglycineM. T. Leplawy, K. Kaczmarek and A. Redlinski

Carboxyl-terminal peptide degradation: Formation of a C-terminal 242

derivative

J.B. Stimmel and G.M. Loudon

On-resin biotinylation of a human interleukin-1 beta analog and its 245

convenient one-step purificationM.R. Deibel, T.J. Lobl, A. W. Yem, D.E. Tracey and J. W. Paslay

Synthetic and physicochemical studies of benzhydrylamine resins with 249

different substitution levels: Implications for solid phase peptide syn¬

thesis

C.R. Nakaie, R. Marchetto, S. Schreier and A. CM. Paiva

Preparation of protected peptides by the solid phase method and HF- 252

stable, but easily removable, blocking groups

W. Neugebauer, G. Champagne, M.-R. Lefebvre andE. Escher

xxi

Contents

Application of trimethylsilyl trifluoromethanesulfonate deprotection 255

procedure for solid phase peptide synthesisM. Nomizu, Y. Inagaki, K. Asano, TV. Fujii, O. Ikemura, A. Otaka

andH. Yajima

Improved linker resin combination for solid phase peptide synthesis 259

M. Mergler, R. Nyfeler, J. Gosteli and P. Grogg

Solid phase synthesis of acid-sensitive peptide amides 261

B. Penke, W. Gray, C.A. Hoeger and J. Rivier

Structure-function relationships in the anemone Stichodactyla helianthus 264

neurotoxin I: Synthesis of native sequence and Glu 8 to Gin analogM. W. Pennington, W.R. Kern andB.M. Dunn

Use of Fmoc amino acid oxobenzotriazine esters in continuous flow 267

low pressure solid phase peptide synthesisE. Atherton, J.C. Glass, B.H. Matthews, G.P. Priestley, J.D. Richards,

P.W. Sheppardand W.A. Wade

Protection of histidine in peptide synthesis: A reassessment of the trityl 270

groupP. Sieber and B. Riniker

A method for solid phase peptide synthesis (SPPS) of C-terminal sulfonic 273

acid peptides: Synthesis of taurinel6-gramicidin AR. W. Roeske and T.P. Hrinyo-Pavlina

Preparation of new amino acids 276

Y. Herve, D.H.R. Barton, J. Thierry and P. Potier

Protease-catalyzed synthesis of oxytocin 279

P. Thorbek, J. Lauridsen and F. Widmer

Protection of side-chain alcoholic hydroxyl groups of serine and threo- 282

nine by the dimethylphosphinyl (Dmp) group

M. Ueki, M. Saito and H. Oyamada

Frhoc-polyamide continuous flow solid phase synthesis of a 74-residue 284

fragment of human /3-chorionic gonadotropinC.-R. Wu, V.C. Stevens, G.W. Tregear and J.D. Wade

Synthesis of human secretin 287

G. Wendlberger, W. Gbhring, G. Hubener, R. Scharf, J. Beythien, Ch.

Beglinger and E. Wiinsch

xxn

Contents

Regiospecific synthesis of [13C-2]-(2S, SSW/ww-epoxysuccinyl-L-leucyl- 289

isoamylamideY. Yabe and D.H. Rich

Convenient synthesis of 2-methyl-3-phenylserine, a sterically hindered 292

a, a-disubstituted amino acid

/. Zabrocki, Z. KaminskiandM.T. Leplawy

Session IV: Mechanism of action

Inositol phosphates and calcium signaling 297

M.J. Berridge

The insulin receptor: A hormone-activated transmembrane tyrosine 302

kinase comprised of two large independently folded soluble domains

L. Ellis

Perturbation-free modification and analysis of functional amino acid 308

residues of a membrane proteinM. Engelhard, B. Hess and F. Siebert

Wasp venom toxin mastoparan, a histamine releaser from mast cells, 310

is a direct activator of GTP-binding regulatory proteinsT. Higashijima, S. Uzu, T. Nakajima and T. Miyazawa

Role of the signal sequence in protein secretion 313

L.M. Gierasch, M.S. Briggs and C.J. McKnighi

Membrane-catalyzed molecular mechanism of tachykinin receptor se- 318

lection

R. Schwyzer, D. Erne, K. Rolka, J. W. Bean and D.F. Sargent

Synthetic peptides identify a critical lysine residue in the SV-40 nuclear 321

transport signalP. Kanda, R. C. Kennedy and R.E. Lanford

Studies on synthetic peptides of small subunit of ribulose 1,5-bisphos- 323

phate carboxylase (RuBisCO)J.V. Edwards, J.M. Bland, D.G. Cornell, T.E. Cleveland, S. Landry

and S. G. Bartlett

Biophysical studies of the fragments of the extension peptide of cy- 325

tochrome P-450 (SCC) precursor

H. Aoyagi, S. Lee, H. Mihara, T. Kanmera and T. Kato

xxiii

Contents

Binding of dynorphin-A-(l-13) and some N-terminal fragments to 328

neutral lipid bilayer membranes

J. W. Bean, D. Erne, D.F. Sargent and R. Schwyzer

Membrane-adjacent regions of receptor proteins 330

CM. Debet; C.J. Brand!, R.B. Deber, L.C. Hsu andX.K. Young

Ionic interactions between substrate side chains and individual subsites 332

in the pepsin active site

J. Pohl andP.M. Dunn

Relationship between the antiviral activity of peptides and the stabi- 335

lization of membrane bilayersR.M. Epand, R.C. McKenzie, D.C. Johnson, T.J. Lobl, H.E. Renis, L.L.

Maggiora andM. W. Wathen

Direct 13C NMR observation of a tetrahedral species in the binding 338

of a peptidyl ketone pseudosubstrate to penicillopepsin, a fungal asparticproteinase

J. Maibaum, M.K. Dhaon, P.G. Schmidt, M. Oka andD.H. Rich

Activities of glucagon antagonists on normal liver: Evidence for cAMP- 341

independent events

R.L. McKee, D. Trivedi, C. Zechel, D. Johnson, K. Brendel and V.J.

Hruby

Crystal structure of the covalent complex formed by a peptidyl a,a- 344

difluoro-/3-keto amide with porcine pancreatic elastase at 1.78 A re¬

solution

L.H. Takahashi, R. Radhakrishnan, E.F. Meyer, Jr. and D.A. Trainor

Session V: Protein design/engineering

Synthetic proteins with a new three-dimensional architecture 349

M. Mutter

Sequence simplification and randomization and the design of peptide 354

recognition surfaces

I. Chaiken, S. Ando, G. Fassina and Y. Shai

A semisynthetic approach to protein engineering: Interleukin-2 rede- 364

signedT.L. Ciardelli, F.E. Cohen, R. Gadski, L. Butler, B. Landgraf and K.A.

Smith

xxiv

Contents

The role of cysteine residues in interleukin-3 function established by 366

total chemical synthesis of analogs/.' Clark-Lewis, L.E. Hood and S.B.H Kent

Cooperativity in multiple amphipathic helical domains ofapolipoprotein 369

A-I

J.P. Segrest, A. Gawish, M. Iqbal, C.G. Brouil/ette, K.B. Gupta and

G.M. Anantharamaiah

Semisynthesis of a deletion mutant of cytochrome c by condensation 372

of enzymatically activated fragmentsC.J.A. Wallace and A.E.I. Proudfoot

Characterization of a two-chain structural variant ofrecombinant human 376

growth hormone

E. Canova-Davis, LP. Baldonado, L.J. Basa, R. Chloupek, T. Doherty,R.J. Harris, R.G. Keck, M.W. Spellman. W.F. Bennett and W.S.

Hancock

Reoxidation of basic reduced insoluble proteins: Example of neurotoxin 379

II of the scorpion Androctonus australis Hector

J.M. Sabatier, H. Darbon, P. Fourquet, H. Rochat andJ. van Rietschoten

Trypsin-catalyzed coupling of synthetic peptides: Semisynthetic produc- 381

tion of phospholipase A2 mutants in high yield/. van Binsbergen, A.J. Slotboom and G.H. de Haas

Protein engineering: Design and synthesis of betabellin 7 383

S.B. Daniels, P.A. Reddy, E. Albrecht, J.S. Richardson, D.C. Richardson

andB.W. Erickson

Phospholipid organization and motion in the presence of model am- 386

phipathic helix-forming peptides with opposite distribution of chargesR.M. Epand, M. Iqbal, A. Gawish, J.P. Segrest, G.M. Anantharamaiah,

W.K. Surewicz and H.H. Mantsch

Simulation of the crystal of Streptomyces griseus protease A 389

D.H. Kitson, F. Avbelj, J. Moult andA.T. Hagler

Synthesis and oxidative properties of cysteine-containing fragments of 392

bovine growth hormone

S.R. Lehrman, T.F. Holzman, C.J. Cole andD.N. Brems

The role of cysteine residues in human interleukin-ly3 396

Y. Masui, T. Kamogashira, Y.-M. Hong, Y. Kikumoto, S. Nakai and

Y. Hirai

XXV

Contents

Synthesis of two component models of elastin 399

K.U. Prasad, M. Iqbal and D.W. Urry

Covalent semisynthesis of a-chain of hemoglobin: Protease-catalyzed 404

transpeptidation at the permissible discontinuity site

A.S. Acharya, Y.J. Cho and G. Sahni

Session VI: Nucleic acid/peptide interactions

The structural basis for activation of trp repressor by L-tryptophan 411

R. W. Schevitz, R.-G. Zhang, C.L. Lawson, Z. Otwinowsky, A. Joachi-

miak and P.B. Sigler

Interaction of peptide antibiotics with DNA 416

T.P. Lybrand

Chemical synthesis of a retroviral nucleic acid binding protein 420

T.D. Copeland, L.E. Henderson, R. Gorelick, Y. Kim and S. Oroszlan

Binding of a thynnine Z-l fragment to DNA 422

F. Marchiori, G. Borin and M. Palumbo

Session VII: Structure-activity relations

Details of the interaction of phosphorus-containing peptide inhibitors 427

with thermolysinP.A. Bartlett, D.H. Drewry, J.E. Hanson and C.K. Marlowe

Design of bradykinin antagonists 433

J.M. Stewart andRJ. Vavrek

Vasopressin agonists and antagonists present distinct pharmacophores 438

at the renal V2 receptor

M.L. Moore and W.F. Huffman

Synthesis and airway smooth muscle relaxant activity of linear and cyclic 441

vasoactive intestinal peptide analogsD.R. Bolin, 7.-7. Sytwu, J.M. Cottrell, R.J. Garippa, C.C. Brooks and

M. O'Donnell

Structure-activity studies of atrial natriuretic factor 444

R.F. Nutt, T.M. Ciccarone, S.F. Brady, CD. Colton, W.J. Paleveda,

T.A. Lyle, T.M. Williams, D.F. Veber, A. Wallace and R.J. Winquist

XXVI

Contents

Characterization of the interaction of thrombin with the C-terminal 447

region of the leech anticoagulant peptide hirudin

J.L. Krstenansky, S.J.T. Mao, T.J. Owen andM.T. Yates

Characterization of parathyroid hormone antagonists 449

L.H. Caporale, M. Chorev, J.J. Levy, M.E. Goldman, P.A. DeHaven,

C.T. Gay, J.E. Reagan, M. Rosenblatt andR.F. Nutt

Angiotensin II. Synthesis and biological activity of 8-(i? and S)- 452

tetrahydroisoquinoline and 1-(R and 5)-(proline)thiazole analogs

P. Balasubramanian and G.R. Marshall

NMR analysis and conformational characterization of cyclic antagonists 457

of gonadotropin-releasing hormone

E.L. Baniak II, L.M. Gierasch, J. Rivier and A.T. Hagler

The a-mating factor of Saccharomyces cerevisiae: A lipopeptide? 459

F. Naider, P. Shenbagamurthi, S. Marcus and J.M. Becker

Receptor-selective somatostatin (SRIF) analogs 462

D.H. Coy, M.L. Heiman, J. Rossowski, W.A. Murphy, J.E. Taylor,

S. Moreau andJ.-P. Moreau

Synthesis and biological activity of novel linear and cyclic GRF analogs 465

A.M. Felix, C.-T. Wang, E. Heimer, A. Fournier, D.R. Bolin, M. Ahmad,

T. Lambros, T. Mowles and L. Miller

Weak oxytocin agonist converted to highly potent oxytocin antagonist 468

through bicyclizationP.S. Hill, J. Slaninova and V.J. Hruby

Synthesis and biological activity of dicarba analogs of vasopressin 471

antagonists

J.F. Callahan, W.F. Huffman, M.L. Moore, N.C.F. Yim, H.G. Bryan,

K.A. Newlander, V. W. Magaard, F. Stassen, L. Kinter, G. Dytko, C.

Albrightson, B. Brickson, N. Caldwell, G. Heckman and D. Schmidt

Renin inhibitors based on novel dipeptide analogs: Increased efficacy 474

through systematic inclusion of polar functionality

D.J. Kempf, E. de Lara, J.J. Planner, H.H. Stein, J. Cohen and H.D.

Kleinert

Tyrosine alone exhibits opiate-like activity when linked to an amphi- 476

pathic hydrocarbon chain

M.A. Khaled, G.M. Anantharamaiah, J.M. Beaton and C.L. Watkins

xxvn

Contents

Functional residues in atriopeptin (103-125)-amide 479

Y. Konishi, R.B. Frazier, G.M. Olins, D.J. Blehm, F.S. Tjoeng, M.E.

Zupec and D.E. Whipple

Tachykinin receptors 482

S. Lavielle, G. Chassaing, J. Besseyre, S. Julien, D. Loeuillet, A.

Marquet, J. C. Beaujouan, L. Bergstrom, Y. Torrens and J. Glowinski

Growth hormone-releasing factor analogs with potent antagonist activity 484

N. Ling, K. Sato, M. Hotta, T.-C. Chiang, H.-Y. Hu and M.-H. Dong

Transition-state analog inhibitors of human renin 487

J.R. Luly, A.K.L. Fung, J.J. Planner, P.A. Marcotte, N. BaMaung,J.L. Soderquist and H.H. Stein

Peptidyl amino steroids as potential new antiarrhythmic agents 490

M. Mokotoff, M. Zhao, Q.-J. Liao, L.K. Wong, W. Barrington and

J. Elson

Contribution of residues B26-B30 to the receptor binding affinities of 494

insulin analogs modified at position Al, A21 or B24

S.H. Nakagawa andH.S. Tager

Development of selective agonists for substance P and neurokinins 497

receptors

G. Drapeau, S. Dion, P. D'Orleans-Juste, N.-E. Rhaleb and D. Regoli

Novel, subnanomolar renin inhibitors containing a postscissile site azide 500

residue

S.H. Rosenberg, K.W. Woods, J.J. Planner, H.H. Stein, H.D. Kleinert

and J. Cohen

Structure-activity relationships of cholecystokinin-8 analogs: Compa- 503

rison of pancreatic, pyloric sphincter and brainstem CCK receptoractivities with in vivo anorexigenic effects

T.K. Sawyer, R.T. Jensen, T. Moran, P.J.K.D. Schreur, D.J. Staples,A.E. deVaux and A. Hsi

Synthesis and activity profiles of bivalent [Leu5]enkephalin-a-oxymor- 505

phamine hybrid opioid receptor ligandsP.W. Schiller, T.M.-D. Nguyen, C. Lemieux, D.L. Larson, G. Ron-

sisvalle, A.E. Takemori and P.S. Portoghese

Structure-function studies in a series of tachykinin antagonists containing 508

a conformationally constrained tryptophan analogB.A. Morgan, J. Singh, E. Baizman, H. Bentley, D. Keifer and S. Ward

xxvni

Contents

Potent in vivo inhibitors of rat renin 510

J. Sueiras-Diaz, D.M. Jones, D.M. Evans, M. Szelke, BJ. Leckie, S.R.

Beattie, E.C.H. Wallace and J.J. Morton

Session VIII: Immunology

Models and mechanisms for the immune recognition of protein antigenic 515

sites by B-cells and T-cells

J.A. Smith

A synthetic strategy for epitope mapping 519

H.M. Geysen, S.J. Rodda and T.J. Mason

Solid phase synthesis of biologically active antigenic peptides for T- 524

cells

LA. Casten, P. Kaumaya, M.S. Anderson, J.A. Smith and S.K. Pierce

Recognition of peptide antigens by T-lymphocytes 527

B. Singh, M. Boyer, Z. Novak, E. Fraga and A. Fotedar

Structure-function relationship in protection against foot and mouth 531

disease (FMD) by a synthetic peptideR. DiMarchi, G. Brooke, C. Gale and T. Doel

Tubulin domains examined by antibodies from synthetic peptides 534

D. Andreu, S. de la Vina and J.M. Andreu

Neutralizing rabbit antibodies to synthetic human interleukin-2 (IL- 537

2) peptidesW. Danho, R. Makofske, J. Swistok, J. Michalewsky, T. Gabriel, J.

Jenson, W.-H. Tsien and M. Gately

Use of synthetic peptides for specific assays of proproteins: Assay of 540

proapolipoprotein A-I

C. Martin, A. Barkia, J.C. Gesquiere, P. Puchois, C. Cachera, J.C.

Fruchart and A. Tartar

The determination of the precise amino acids involved, and their relative 543

importance, in peptide antigen/monoclonal antibody interactions

R.A. Houghten, JR. Appel and J.M. Sitarik

Synthesis of glycopeptides with tumor-associated antigen structure 547

H. Kunz, S. Friedrich-Bochnitschek and S. Birnbach

xxtx

Contents

Formation of amphipathic secondary structure is correlated to T-cell 549

antigenicity in a series ofsynthetic peptides from sperm whale myoglobinL.R. Sanza, L.M. Gierasch, J.A. Berzofsky, G.K. Buckenmeyer, K.B.

Cease and C.S. Ouyang

Manipulation of the immune response against a peptide from the C- 551

terminal part of the surface protein VP1 of foot and mouth disease

virus

W.M.M. Schaaper, W.C. Puijk, D.J.A. Meijer, H. Lankhof, W.P.A.

Posthumus andR.H. Meloen

Mimicking protective epitopes of foot and mouth disease virus with 553

synthetic peptidesA.Yu. Surovoy, O.M. Vol'pina, V.M. Gelfanov and V.T. Ivanov

Characterization of antibody binding sites using peptides synthesized 555

on aminomethyl-resinW.-J. SyuandL. Kahan

Session IX: Growth factors/oncogenes

Structure-activity studies of transforming growth factor 561

J.P. Tarn

Peptide substrates and inhibitors of TV-myristoyl transferase 566

S.R. Eubanks, D.S. Towery, F.S. Tjoeng, S.P. Adams, D.A. Towler,E. Jackson-Machelski, L. Glaser and J.L Gordon

Analysis of the interaction of IGF I and structural mutants of IGF 570

I with the IGF types 1 and 2 and insulin receptorsM.A. Cascieri, G.G. Chicchi, B.G. Green, J. Applebaum, N.S. Hayesand M.L. Bayne

Conformational studies of N-terminal segments ofras p21 proteins 572

C.-H. Niu, K. Han and P.P. Roller

Third loop analogs of epidermal growth factor: Bioassay studies for 575

receptor affinity and tyrosine kinase activation

T.J. Lobl, L.L. Maggiora andJ.W. Wilks

Purification and analysis of a hepatocyte antiproliferative glyc'opeptide 578

G. Auger, D. Blanot, G.A. Boffa, M.-F. Gournay, J. Van Heijenoort,P. Lambin, P. Maes, C. Nadal andA. Tartar

xxx

Contents

Structures of human TGFa fragments using two-dimensional proton 581

magnetic resonance spectroscopy and computer simulation

K. Han, C.-H. Niu, B.R. Brooks, J. A. Ferretti and P.P. Roller

A comparative study of strategy and cleavage and methods by HF and 584

trifluoromethanesulfonic acid: Synthesis ofShope fibroma growth factor

and proteoglycan growth factor

D.-X. Wang, Y.-Z. Lin. G. Caporaso, P.-Y. Chang, X.-H. Ke and LP.

Tarn

Substrates of tyrosine-specific protein kinase: Synthetic peptides derived 587

from lipocortinsR.G. Yarger, R.H. Berg, S.A. Rotenbergand J.P. Tarn

Session X: Neurochemistry

Receptor-mediated peptide transport through the blood-brain barrier 593

W.M. Pardridge

Neuropeptide co-transmitters in physiologically identified motor neu- 596

rons in AplysiaP.E. Lloyd and D.P. Lotshaw

Distinct endogenous ligands for PCP and sigma opioid receptors 601

D.A. DiMaggio, P.C. Contreras andT.L. 0'Donahue

Comparison of amyloid from Alzheimer's disease with synthetic peptide 604

L.K. Duffy, D.A. Kirschner, C.L. Joachim, A. Sinclair, H. lnouye and

D.J. Selkoe

Cyclic CCK-8 analogs highly selective for central receptors 608

B. Charpentier, I. Marseigne, A. Dor, D. Begue, C. Durieux, D. Pelaprat,M. Reibaud, J.L. Zundel, J.C. BlanchardandB.P. Roques

Structural requirements for the satiety effect of CCK-8 610

J.D. Rosamond, J.M. Comstock, N.J. Thomas, A.M. Clark, J. C. Blosser,R.D. Simmons, D.L. Gawlak, M.E. Loss, S.J. Augello-Vaisey, A.F.

Spatola andD.E. Benovitz

A study of the substrate specificity of carboxypeptidase H 613

N.J. Darby, L.D. Fricker, K. Maruthainar and D. G. Smyth

xxxi

Contents

Relationship between the conformational properties of a new series of 615

hexapeptides derived from DSLET and DTLET and their opioid delta

selectivityM.-C. Fournie-Zaluski, J. Belleney, G. Gacel, B. Maigret and B.P.

Roques

Interaction of the dogfish cyclic tachykinin scyliorhinin II with tachy- 617

kinin NK-1 and NK-2 binding sites

J.L. Krstenansky and S.H. Buck

Theoretical conformational analysis of ju-selective cyclic opioid peptide 619

analogsB.C. Wilkes and P. W. Schiller

Session XI: New biological areas

Peptide sequences specified by complementary RNAs represent binding 623

sites for proteins or peptides which interact

K.L. Bost and J.E. Blalock

Didemnin and its biological properties 626

K.L. Rinehart

Identification of two distinct regions of an alternatively spliced site in 632

human plasma fibronectin that promotes cell-type specific adhesion

M.J. Humphries, A. Komoriya, S.K. Akiyama, K. Olden and KM.

Yamada

Melanin-concentrating hormone: Structure-activity studies of a new 635

hormone

M.E. Hadley, A.M.L. Castrucci and V.J. Hruby

Synthesis and biological activity of peptides inhibiting herpes simplex 638

virus ribonucleotide reductase

P. Gaudreau, J. Michaud, S. Rakhit, J.-M. Ferland, J. Gauthier, Y.

Langelier and P. Brazeau

The synthesis and characterization of 81- and 88-residue peptides: 641

Conserved structures in the protein components ofcartilage proteoglycanaggregates

P.J. Neame, G.M. Anantharamaiah, J.E. Christner and J.R. Baker

Glucagonlike peptide I (7-37) is a potent stimulator of insulin secretion 644

S. Mojsov, G.C. Weir and J.F. Habener

xxxn

Contents

The design and testing of specific inhibitors of tissue kallikrein: Role 647

of the enzyme in blood pressure regulationJ. Burton

Detection of new peptaibol antibiotics (mycotoxins) in species and strains 650

of the fungal genus Trichoderma

H. Bruckner, C. Kussin and T. Kripp

Structure-activity relationships for insect hypertrehalosemic hormone: 653

The importance of side chains and termini

M.M. Ford, T.K. Hayes andL.L. Keeley

Structure elucidation of the major cytotoxic component of Trididemnum 656

cyanophorumB. Castro, P. Jouin, A. Cave, M. Dufour, B. Banaigs and C. Fransisco

Backbone modification of synthetic poly-a-L-amino acids 658

/. Kohn and R. Longer

Peptide derivatives specific for a Plasmodiumfalciparum protease involv- 662

ed in red blood cell invasion by merozoites

R. Mayer, I. Picard, F. Bernard, P. Lawton, P. Grellier, J. Schrevel

and M. Monsigny

Author index 664

Subject index 673

xxxiii