Total synthesis of the potent proteasome inhibitor epoxomicin: a useful tool for understanding proteasome biology.

Abstract

Epoxomicin (1), a peptide alpha',beta'-epoxyketone isolated from the actinomycete strain No.Q996-17, possesses potent in vivo anti-tumor and anti-inflammatory activities. In this paper, we report the first syntheses of epoxomicin, [3H]-epoxomicin, and a biotinylated epoxomicin analog as well as the absolute configuration of the epoxide stereocenter. The natural product and derivatives have permitted the first identification of the proteasome as the specific cellular target of epoxomicin.

• Authors: N Sin, K B Kim, M Elofsson, L Meng, H Auth, B H Kwok, C M Crews
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 9 Issue 15 Pg. 2283-8 (Aug 02 1999) ISSN: 0960-894X [Print] England
• PMID: 10465562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antibiotics, Antineoplastic
• Enzyme Inhibitors
• Multienzyme Complexes
• Oligopeptides
• Receptors, Drug
• Cysteine Endopeptidases
• Proteasome Endopeptidase Complex
• epoxomicin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, pharmacology)
• Antibiotics, Antineoplastic (chemical synthesis, pharmacology)
• Biotinylation
• Cysteine Endopeptidases (drug effects, metabolism)
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Mice
• Multienzyme Complexes (drug effects, metabolism)
• Oligopeptides (chemical synthesis, pharmacology)
• Proteasome Endopeptidase Complex
• Receptors, Drug (isolation & purification)
• Tumor Cells, Cultured