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Antibiotic Puromycin ----An inhibitor of protein synthesis

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.

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Antibiotic Puromycin ----An inhibitor of protein synthesis

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  1. Antibiotic Puromycin ----An inhibitor of protein synthesis Ping Jiang 03-05-2000

  2. Outline • Discovery and Properties • Structure and Functions • Molecular Mechanism of Action • Analogues and Synthesis • Applications and Prospect

  3. Discovery 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

  4. Chemical Properties Formula: C22H29N7O5, 2HCl; MW: 544.2 pKa: 6.8 and 7.2 Puromycin is suitable for research purposes only. It must not be used on humans. http://www.cayla.com/support/datasheets/protect.htm

  5. Structure Puromycin: a structural and a functional analogue of 3’ terminus of aminoacyl-tRNA The Ribosome: Structure, Function, and Evolution. 1990

  6. 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 • Functions RNA, 2000, 6, 744-754; Inhibitors of Protein Synthesis, 1979

  7. Binding Translocation Transpeptidation • Mechanism:

  8. Nascent Protein Release A site P site tRNA puro 5’ Stop coden mRNA Ribosome • Mechanism: Nature,1963, 197, 1067-1977; FEBS Lett., 1997, 406, 223-233

  9. Mechanism: The Molecular Basis of Antibiotic Action, 1972, 412

  10. Analogues and Synthesis: A rich array ofpuromycin 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

  11. Analogues and Synthesis: Bioorg. & Medicinal Chem., 1995, 3, 1631-1636

  12. Analogues and Synthesis: J. Org. Chem., 2001, 66, 8204-8210

  13. 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. • Applications and Prospect: Nucleic Acid Research, 2000, 28, 1176-1182

  14. Full length Protein Release A site P site tRNA puro 5’ Stop coden mRNA Ribosome • Application and Prospect: Nucleic Acid Research, 2000, 28, 1176-1182

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