Format

Send to

Choose Destination
See comment in PubMed Commons below
Org Biomol Chem. 2012 Jan 7;10(1):181-94. doi: 10.1039/c1ob06554h. Epub 2011 Nov 22.

Discovery of a potent and highly β1 specific proteasome inhibitor from a focused library of urea-containing peptide vinyl sulfones and peptide epoxyketones.

Author information

  • 1Gorlaeus Laboratories, Einsteinweg 55, 2300 CC, Leiden, The Netherlands.

Abstract

Syringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureido structural element present in syringolins is incorporated in oligopeptide vinyl sulfones and peptide epoxyketones yielding a focused library of potent new proteasome inhibitors. The distance of the ureido linkage with respect to the electrophilic trap strongly influences subunit selectivity within the proteasome. Compounds 13 and 15 are β5 selective and their potency exceeds that of syringolin A. In contrast, 5 may well be the most potent β1 selective compound active in living cells reported to date.

PMID:
22105930
PMCID:
PMC3769973
DOI:
10.1039/c1ob06554h
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Royal Society of Chemistry Icon for PubMed Central
    Loading ...
    Support Center