Proteasome selectivity towards Michael acceptor containing oligopeptide-based inhibitors

Publication Type:

Journal Article

Authors:

van der Linden, W.A.; Geurink, P.P.; Oskam, C.; van der Marel, G.A.; Florea, B. I; Overkleeft, H.S.

Source:

Org Biomol Chem, Volume 8, Number 8, p.1885-93 (2010)

ISBN:

1477-0539 (Electronic)14

DOI Name (links to online publication)

10.1039/b924134e

Abstract:

The synthesis and biological evaluation of ten Michael acceptors containing potential proteasome inhibitors are described. Cellular targets of azide containing inhibitors and were assessed in HEK293T and RAW264.7 cells by a two step labeling strategy, followed by biotin-pulldown, affinity purification, on-bead tryptic digestion and LC-MS(2) identification. This strategy appears to be an attractive alternative to gel-based competition assays.