Abstract
The proteasome regulates diverse intracellular processes, including cell-cycle progression, antigen presentation, and inflammatory response. Selective inhibitors of the proteasome have great therapeutic potential for the treatment of cancer and inflammatory disorders. Natural cyclic peptides TMC-95A and B represent a new class of noncovalent, selective proteasome inhibitors. To explore the structure-activity relationship of this class of proteasome inhibitors, a series of TMC-95A/B analogues were prepared and analyzed. We found that the unique enamide functionality at the C-8 position of TMC-95s can be replaced with a simple allylamide. The asymmetric center at C-36 that distinguishes TMC-95A from TMC-95B but which necessitates a complicated separation of the two compounds can be eliminated. Therefore, these findings could lead to the development of more accessible simple analogues as potential therapeutic agents.
Original language | English (US) |
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Pages (from-to) | 508-513 |
Number of pages | 6 |
Journal | ChemBioChem |
Volume | 4 |
Issue number | 6 |
DOIs | |
State | Published - Jun 6 2003 |
Externally published | Yes |
Keywords
- Inhibitors
- Peptides
- Proteasome
- Structure-activity relationships
- Synthesis
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Organic Chemistry