Novel photochromic inhibitor for mitotic kinesin Eg5 which forms multiple isomerization states
| Autor: | Shinsaku Maruta, Islam M D Alrazi, Kei Sadakane |
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| Rok vydání: | 2020 |
| Předmět: |
Indoles
Cell division Light ATPase Kinesins Mitosis 010402 general chemistry 01 natural sciences Biochemistry Microtubules 03 medical and health sciences chemistry.chemical_compound Photochromism Isomerism Cell Movement Humans Merocyanine Benzopyrans Molecular Biology 030304 developmental biology Spiropyran Adenosine Triphosphatases 0303 health sciences Luminescent Agents biology Chemistry General Medicine Nitro Compounds 0104 chemical sciences Biophysics biology.protein Kinesin Isomerization Azo Compounds Cell Division Protein Binding |
| Zdroj: | Journal of biochemistry. 170(2) |
| ISSN: | 1756-2651 |
| Popis: | The mitotic kinesin Eg5 is a plus-end directed homotetrameric molecular motor essential for the formation of bipolar spindles during cell division. Kinesin Eg5 is overexpressed in cancer cells and hence considered as a target for cancer therapy; the inhibitors specific for Eg5 have been developed as anticancer drugs. In this study, we synthesized a novel functional photoresponsive inhibitor composed of spiropyran and azobenzene derivatives to control Eg5 function with multistage inhibitory activity accompanied by the formation of different isomerization states. The photochromic inhibitor spiropyran-sulfo-azobenzene (SPSAB) exhibited three isomerization states: spiro (SP)-trans, merocyanine (MC)-cis and MC-trans, upon exposure to visible light, ultraviolet and in the dark, respectively. SPSAB-induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with photoisomerization among the three states. Among the three isomerization states of SPSAB, the SP-trans isomer showed potent inhibitory activity at an IC50 value of 30 µM in the basal ATPase assay. MC-trans and MC-cis exhibited less inhibitory activity at IC50 values of 38 and 86 µM, respectively. The results demonstrated that the novel photochromic inhibitor enabled precise control of Eg5 function at three different levels using light irradiation. |
| Databáze: | OpenAIRE |
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