Abstract:
:Mitotic kinesin Eg5 plays an important physiological role in cell division. Several small-molecule inhibitors of Eg5 are the focus of cancer therapies. Azobenzene is a photochromic compound exhibiting cis-trans isomerization upon ultraviolet (UV) and visible (VIS) light irradiation. Photochromic compounds of azobenzene derivatives, mimicking Eg5-specific inhibitors of STLC, indicated photoreversible inhibitory effects on Eg5 ATPase activity; however, the photoreversible switching efficiency was not significant. This study presents a novel synthesized photochromic Eg5 inhibitor 2, 3-bis[(2,5-dioxo-1-{4-[(E)-2-phenyldiazen-1-yl]phenyl}pyrrolidin-3-yl)sulfanyl] butanedioic acid (BDPSB), which is composed of two azobenzenes. BDPSB exhibited cis-trans isomerization with UV and VIS light irradiation. The trans form of BDPSB significantly inhibited microtubule-dependent ATPase activity of Eg5, with an IC50 of 74 μM. Cis BDPSB showed weak effects on the microtubule-dependent ATPase activity. The results suggest that the novel photochromic Eg5 inhibitor BDPSB, which exhibits highly efficient photoswitching, shows a switch 'ON' and 'OFF' behaviour with VIS and UV light irradiation.
journal_name
J Biochemjournal_title
Journal of biochemistryauthors
Sadakane K,Alrazi IMD,Maruta Sdoi
10.1093/jb/mvy051subject
Has Abstractpub_date
2018-10-01 00:00:00pages
295-301issue
4eissn
0021-924Xissn
1756-2651pii
5025987journal_volume
164pub_type
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