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.
Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Tokyo 171-8588, Japan. hiroyuki.nakamura@gakushuin.ac.jp
Hiroyuki
H
Nakamura
Mizuyoshi
M
Watanabe
Hyun Seung
HS
Ban
Wataru
W
Nabeyama
Akira
A
Asai
D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D001895:Boron; D002918:Chymotrypsin; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010455:Peptides; D061988:Proteasome Inhibitors; C406054:belactosin C; D002918:Chymotrypsin; D001895:Boron