title: Tubulin photoaffinity labeling study with a plinabulin chemical probe possessing a biotin tag at the oxazole.
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.
authors.affiliation: Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Yui
authors.initials: Y
authors.lastname: Kido
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
authors.forename: Fumika
authors.initials: F
authors.lastname: Yakushiji
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D001710:Biotin / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D015335:Molecular Probes; D010080:Oxazoles / Q000737:chemistry*; D019920:Photoaffinity Labels; D014404:Tubulin / Q000737:chemistry*
chemical_list: D015335:Molecular Probes; D010080:Oxazoles; D019920:Photoaffinity Labels; D014404:Tubulin; D001710:Biotin