Hensens O D, Chin D H, Stassinopoulos A, Zink D L, Kappen L S, Goldberg I H
Natural Products Chemistry Department, Merck Research Laboratories, Rahway, NJ 07065.
Proc Natl Acad Sci U S A. 1994 May 10;91(10):4534-8. doi: 10.1073/pnas.91.10.4534.
Detailed structure determination of the major and minor base-catalyzed degradation products of the chromophore of the enediyne anticancer antibiotic neocarzinostatin in the absence of DNA demonstrates that the enolate Michael addition reaction leading to a spirolactone cumulene intermediate is a spontaneous, stereoselective process. The implications of these findings for the mechanism of the thiol-independent, site-specific cleavage by the so-generated radical species of the drug at a DNA bulge are described.
在无DNA的情况下，对烯二炔类抗癌抗生素新制癌菌素发色团的主要和次要碱催化降解产物进行详细的结构测定，结果表明，导致螺内酯累积二烯中间体的烯醇负离子迈克尔加成反应是一个自发的立体选择性过程。本文描述了这些发现对于该药物由此产生的自由基物种在DNA凸起处进行不依赖硫醇的位点特异性切割机制的意义。
