Synthesis and biological evaluation of boron peptide analogues of Belactosin C as proteasome inhibitors

A series of boron peptides 11, 13, 15 and 17 were designed and synthesized as proteasome inhibitors based on the structure of Belactosin C. Matteson homologation was a key step in the synthesis of the boron peptides. Compounds 11a and 13 showed significant inhibition of 20S proteasome chymotrypsin-like (beta 5) activity (IC(50) = 0.28 and 0.51 mu M, respectively). Furthermore, like PS-341, compound 11a increased the G2/M cell distribution. A biparametric cytofluorimetric analysis with FITC-labeled annexin V and propidium iodide showed induction of apoptosis by compound 11a at >1 mu M concentrations of compound. (C) 2009 Elsevier Ltd. All rights reserved.