1. Tubulin photoaffinity labeling study with a plinabulin chemical probe possessing a biotin tag at the oxazole.
- Author
-
Yamazaki Y, Kido Y, Hidaka K, Yasui H, Kiso Y, Yakushiji F, and Hayashi Y
- Subjects
- HT29 Cells, Humans, Biotin chemistry, Molecular Probes, Oxazoles chemistry, Photoaffinity Labels, Tubulin chemistry
- Abstract
A new bioactive photoaffinity probe KPU-252-B1 (4) possessing a biotin tag on the oxazole ring of a potent plinabulin derivative KPU-244 (2) was synthesized via the Cu(I)-catalyzed Huisgen's cycloaddition reaction to understand the precise binding mode of the diketopiperazine-based anti-microtubule agent plinabulin on tubulin. Probe 4 showed significant binding affinity toward tubulin and cytotoxicity against an HT-29 cells. A photoaffinity labeling study suggested that probe 4 specifically recognizes tubulin at a binding site that binds plinabulin or colchicine, most likely near or at the colchicine binding site, which is located at the interfacial region formed by α-and β-tubulin association. The results also demonstrated that probe 4 may serve as a useful plinabulin chemical probe to investigate the molecular mechanism by which anti-microtubule diketopiperazine derivatives operate., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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