Highly efficient photocontrol of mitotic kinesin Eg5 ATPase activity using a novel photochromic compound composed of two azobenzene derivatives
Highly efficient photocontrol of mitotic kinesin Eg5 ATPase activity using a novel photochromic compound composed of two azobenzene derivatives
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使用由两种偶氮苯衍生物组成的新型光致变色化合物对有丝分裂驱动蛋白 Eg5 ATPase 活性进行高效光控制
DOI：
10.1093/jb/mvy051
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
S. Maruta
中科院分区：
文献类型：
--
作者：
Kei Sadakane;I. M. Alrazi;S. Maruta
有丝分裂驱动蛋白Eg 5在细胞分裂中起重要的生理作用。Eg 5的几种小分子抑制剂是癌症治疗的焦点。偶氮苯是一种光致变色化合物，在紫外光（UV）和可见光（维斯）照射下表现出顺反异构化。偶氮苯衍生物的光致变色化合物，模仿Eg 5-特异性抑制剂的STLC，表明光可逆的抑制作用Eg 5 ATP酶的活性，但是，光可逆的转换效率是不显着的。本研究合成了一种新型的光致变色Eg 5抑制剂2，3-二[（2，5-二氧代-1-{4-[（E）-2-苯基二氮烯-1-基]苯基}吡咯烷-3-基）硫基]丁二酸（BDPSB），它由两个偶氮苯组成。BDPSB在紫外和维斯光照射下表现出顺反异构化。BDPSB的反式可显著抑制Eg 5的微管依赖性ATP酶活性，IC 50为74 μM。顺式BDPSB对微管依赖性ATP酶活性的影响较弱。结果表明，新型光致变色Eg 5抑制剂BDPSB，这表现出高效的光开关，显示开关“ON”和“OFF”的行为与维斯和UV光照射。
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.
DOI：
10.1073/pnas.85.17.6314
发表时间：
1988-09-01
影响因子：
11.1
作者：
HACKNEY, DD
通讯作者：
HACKNEY, DD
影响因子：
16.6
作者：
Catarinella, Mario;Gruener, Tamara;Mayer, Thomas U.
通讯作者：
Mayer, Thomas U.