Computational predictions of corroles as a class of Hsp90 inhibitors.
Computational predictions of corroles as a class of Hsp90 inhibitors.
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DOI：
10.1039/c5mb00352k
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发表时间：
2015-10
影响因子：
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通讯作者：
R. D. Teo;Sijia S. Dong;Z. Gross;H. Gray;W. Goddard
中科院分区：
文献类型：
--
作者：
R. D. Teo;Sijia S. Dong;Z. Gross;H. Gray;W. Goddard
相关作用已被实验证明可导致细胞周期停滞，有证据表明这可能归因于腐蚀对热休克蛋白90(Hsp90)的抑制作用，Hsp90被认为在癌细胞增殖中起着至关重要的作用。在本研究中，我们用分子动力学研究了镓腐蚀剂与Hsp90的相互作用，发现它们可以优先结合到ATP结合的N-末端。我们还发现，Corole环的结构变化会影响Corole与Hsp90的结合能和亲和力。我们预测，双羧化考罗(4-Ga)和建议的3，17-双磺化考罗(7-Ga)都有望替代Ga(III)5，10，15-tris(pentafluorophenyl)-2，17-bis(sulfonic考罗(1-Ga)作为抗癌药物。
Corroles have been shown experimentally to cause cell cycle arrest, and there is some evidence that this might be attributed to an inhibitory effect of corroles on Heat shock protein 90 (Hsp90), which is known to play a vital role in cancer cell proliferation. In this study, we used molecular dynamics to examine the interaction of gallium corroles with Hsp90, and found that they can bind preferentially to the ATP-binding N-terminal site. We also found that structural variations of the corrole ring can influence the binding energies and affinities of the corrole to Hsp90. We predict that both the bis-carboxylated corrole (4-Ga) and a proposed 3,17-bis-sulfonated corrole (7-Ga) are promising alternatives to Ga(III) 5,10,15-tris(pentafluorophenyl)-2,17-bis(sulfonic acid)-corrole (1-Ga) as anti-cancer agents.