Hill G C, Wunz T P, Remers W A
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson 85721.
J Comput Aided Mol Des. 1988 Jul;2(2):91-106. doi: 10.1007/BF01532085.
Computer-based models were derived for the covalent and noncovalent binding of the antitumor antibiotic quinocarcin to a representative DNA segment, d(ATGCAT)2. They showed that a mode of action, involving opening of the oxazolidine ring to give an iminium ion, followed by initial noncovalent binding in the minor groove and subsequent alkylation of the 2-amino group of guanine, was rational and attended by favorable interaction energies in each step. The best model had the aryl ring of quinocarcin lying in the 3' direction from the covalent binding site and an R configuration at the carbon involved in covalent bond formation. It also showed that the preferred absolute configuration for quinocarcin was the reverse of that arbitrarily assigned in the literature.
基于计算机的模型推导了抗肿瘤抗生素醌癌菌素与代表性DNA片段d(ATGCAT)2的共价和非共价结合情况。结果表明，一种作用模式是合理的，即恶唑烷环打开生成亚胺离子，随后在小沟中进行初始非共价结合，接着鸟嘌呤的2-氨基发生烷基化，且每一步都有良好的相互作用能。最佳模型显示，醌癌菌素的芳环位于共价结合位点的3'方向，且在形成共价键的碳原子上具有R构型。该模型还表明，醌癌菌素的优选绝对构型与文献中任意指定的构型相反。
