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 (beta5) activity (IC(50)=0.28 and 0.51 microM, 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 microM concentrations of compound.