NMR and molecular modeling study of the conformations of taxol 2'-acetate in chloroform and aqueous dimethyl sulfoxide solutions.
NMR and molecular modeling study of the conformations of taxol 2'-acetate in chloroform and aqueous dimethyl sulfoxide solutions.
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氯仿和二甲基亚砜水溶液中紫杉醇 2-乙酸酯构象的核磁共振和分子模型研究。
DOI：
10.1021/jm950796q
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发表时间：
1996
影响因子：
7.3
通讯作者：
Williams,DK
中科院分区：
文献类型：
--
作者：
Williams,HJ;Moyna,G;Scott,AI;Swindell,CS;Chirlian,LE;Heerding,JM;Williams,DK
紫杉醇2‘-乙酸酯是一种抗肿瘤药物紫杉醇的类似物，在体外没有显示出显著的微管聚合活性，因此强调了自由2’-羟基对紫杉醇生物活性的重要性。以前的工作表明，紫杉醇2‘-乙酸酯的失活不是由于乙酰基的空间干扰。本研究考察了紫杉醇2‘-乙酸酯在重碘氯仿和2H2O−重碘甲基亚砜溶液中的构象，发现它们与紫杉醇本身采用的构象基本相同。因此，似乎既不可能通过乙酰基破坏紫杉醇活性构象的不稳定，也不可能形成2‘-OH基团的重要紫杉醇构象决定作用。这些发现意味着紫杉醇2‘-OH基团直接与紫杉醇−微管复合体中的蛋白质残基相互作用，可能是作为氢键供体。
Taxol 2‘-acetate, an analog of the antitumor drug taxol, displays no significant in vitro microtubule polymerization activity, thus underscoring the importance of a free 2‘-OH group to the biological activity of taxol. Previous work had suggested that the inactivity of taxol 2‘-acetate is not due to steric interference by the acetyl group. The present study examined the conformations of taxol 2‘-acetate in deuteriochloroform and2H2O−deuteriodimethyl sulfoxide solutions and found them to be essentially the same as the respective conformations adopted by taxol itself. Thus, neither destabilization of an active taxol conformation by the acetyl group nor the formation of an important taxol conformation determining role for the 2‘-OH group appears likely. The implication of these findings is that the taxol 2‘-OH group interacts directly with a protein residue in the taxol−microtubule complex, perhaps as a hydrogen bond donor.