Back to Search
Start Over
Tubulin photoaffinity labeling study with a plinabulin chemical probe possessing a biotin tag at the oxazole
- Source :
-
Bioorganic & Medicinal Chemistry . Jan2011, Vol. 19 Issue 1, p595-602. 8p. - Publication Year :
- 2011
-
Abstract
- 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 CuI-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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 19
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 57251758
- Full Text :
- https://doi.org/10.1016/j.bmc.2010.10.055