antibiotic puromycin ----an inhibitor of protein synthesis
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Antibiotic Puromycin ----An inhibitor of protein synthesis. Ping Jiang 03-05-2000. Outline. Discovery and Properties Structure and Functions Molecular Mechanism of Action Analogues and Synthesis Applications and Prospect. Discovery. - PowerPoint PPT PresentationTRANSCRIPT
Antibiotic Puromycin
----An inhibitor of protein synthesis
Ping Jiang
03-05-2000
Outline
• Discovery and Properties
• Structure and Functions
• Molecular Mechanism of Action
• Analogues and Synthesis
• Applications and Prospect
In 1952, the new antibiotic, Puromycin , isolated from the mold Streptomyces alboniger, has been found to be active against certain bacteria and Trypanosomes in Lederle laboratories division, American Cyanamid Company during the course of their antibiotic-screening program. One year later, the structure of puromycin was determined.
Discovery
Antibiotics and Chemotherapy, 1952, 2, 409
J. Am. Chem. Soc., 1953, 75, 2025
Chemical Properties
Formula: C22H29N7O5, 2HCl;
MW: 544.2
pKa: 6.8 and 7.2
http://www.cayla.com/support/datasheets/protect.htm
Puromycin is suitable for research purposes only.It must not be used on humans.
Structure
Puromycin: a structural and a functional analogue of
3’ terminus of aminoacyl-tRNA
The Ribosome: Structure, Function, and Evolution. 1990
Functions
Many antibiotics target the ribosome.
Puromycin tricks the ribosome into incorporating itself into the growing polypeptide chain causing premature termination, acting as an inhibitor of peptidyl transferase.
The antibiotic inhibits the growth of Gram positive bacteria and various animal and insect cells. Fungi and Gram negative are resistant due to the low permeability of the antibiotic
Problem: it kills eukaryotics and prokaryotics alike
RNA, 2000, 6, 744-754; Inhibitors of Protein Synthesis, 1979
Binding
TranspeptidationTranslocation
Mechanism:
Mechanism:
puro
A siteP site
Nascent
ProteinRelease
5’
mRNAStopcoden
Ribosome
tRNA
Nature,1963, 197, 1067-1977; FEBS Lett., 1997, 406, 223-233
Mechanism:
The Molecular Basis of Antibiotic Action, 1972, 412
Analogues and Synthesis:
A rich array of puromycin analogues with modified amino acid, carbohydrate, and/or base moieties has been prepared and evaluated biologically to study the structure-activity correlations…..
Puromycin (1) and the N-acetylglucosaminyl asparagine-substitued puromycin analogue 2a-c
Analogues and Synthesis:
Bioorg. & Medicinal Chem., 1995, 3, 1631-1636
Analogues and Synthesis:
J. Org. Chem., 2001, 66, 8204-8210
Applications and Prospect:
Puromycin has been widely used as a basic tool for studying protein synthesis.
Now, puromycin hydrochloride is particularly useful for the selection of cell types harbouring plasmids carrying puromycin resistance genes.
The specific bonding of puromycin to full-length protein at the C-terminus at a low concentration is potentially useful to the analysis of various biological phenomena.
Nucleic Acid Research, 2000, 28, 1176-1182
Application and Prospect:
puro
A siteP site
Release
5’
mRNA Stopcoden
Ribosome
tRNA
Full lengthProtein
Nucleic Acid Research, 2000, 28, 1176-1182