Development of photochromic anti-cancer agent : kinesin Eg5 inhibitor

真核细胞分裂过程中，有丝分裂运动蛋白Eg5对双极纺锤体的形成至关重要，被认为是治疗癌症的潜在靶点。STLC是一种抑制Eg5的分子机制已被研究得很透彻的抑制剂。在这项研究中，我们合成了一种新型的光致变色STLC类似物ACTAB，它由三基基、偶氮苯和乙酰半胱氨酸组成，通过顺反光异构化来光控制Eg5的功能。ACTAB在两种不同可见波长的交替照射下表现出顺-反光异构化。ACTAB诱导与顺反光异构化相关的atp酶抑制活性和运动活性可逆变化。与顺式actab相比，反式actab更显著地降低了ATPase活性和微管滑动速度。这些结果表明ACTAB可以作为Eg5的光致变色抑制剂来实现对活细胞的光调控。

The mitotic kinesin Eg5 is essential for the formation of bipolar spindles during eukaryotic cell division, it has been considered as a potential target for cancer treatment. STLC is one of the inhibitors of Eg5 whose molecular mechanism of inhibition was well studied. In this study, we synthesized a novel photochromic STLC analogues, ACTAB, composed of a trityl group, azobenzene, and Acetyl-L-cysteine, which exhibits cis-trans photoisomerization in order to photocontrol the function of Eg5. ACTAB exhibited cis-trans photoisomerization upon alternating irradiation at two different visible wavelengths. ACTAB induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with the cis-trans photoisomerization. Compared to cis-ACTAB, trans-ACTAB reduced ATPase activity and microtubule gliding velocity more significantly. These results suggest that ACTAB could be used as photochromic inhibitor of Eg5 to achieve photocontrol of living cells.