The Journal of Biochemistry · 2018 · 12 citations · 20 references
Life SciencesCell BiologyMolecular BiologyBiophotonicsCytoskeletonMolecular BiophysicsMicrotubule-based TransportMitotic InhibitorsMotor ProteinsPhotochemistryKinesin BiochemistryKinesin FunctionKinesin InhibitorsPhotophysical MechanismsPhotosensitizersPhotosensitizing CompoundsReversible Conformational ChangesSpiropyran Compounds
In this study, we synthesized a novel photochromic inhibitor of the mitotic kinesin Eg5, which is composed of the photochromic compound spiropyran to photo-control the function of Eg5. The compound (S)-2, 3-dispiropyran propionic acid (DSPPA) exhibits reversible spiropyran-merocyanine photo-isomerization upon irradiation with visible or ultra-violet light. DSPPA induced reversible changes in the inhibitory effect on Eg5 ATPase and motor activities, which correlates with the spiropyran-merocyanine photo-isomerization. Microtubule-dependent ATPase activity was significantly more inhibited by the spiropyran isomer of DSPPA than by the merocyanine isomer. Additionally, an in vitro motility assay revealed that the microtubule gliding velocity was reduced more by the spiropyran isomer than by the merocyanine isomer. This indicates that the spiropyran derivative may be useful in regulating the function of the mitotic kinesin.
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Antitumor Activity of a Kinesin Inhibitor
Roman Sakowicz, Jeffrey T. Finer, Christophe Béraud et al. · Cancer Research · 2004 · 241 citations