Rao S N
Searle Research and Development, Division of G.D. Searle and Co., Skokie, Illinois 60077.
Biochem Biophys Res Commun. 1990 Mar 16;167(2):477-83. doi: 10.1016/0006-291x(90)92048-5.
Molecular mechanics simulations have been presented on the covalent complexes between anthramycin and the decanucleotides d(GCGCGCGCGC)2 and d(GCGCGTGCGC).d(GCGCACGCGC) in the novel Z form, with the drug docked in the minor groove. The simulations predict that anthramycin binds to Z-DNA almost as well as it does to B-DNA, but with a few key differences in the structural aspects of binding. In particular, the 5' orientation of the drug is preferred in the Z form, contrasting with the preference for 3' orientation in the B form and the drug has a left-handed twist. While no experimental studies have been published on the binding of pyrrolo(1,4)benzodiazepines to left-handed forms of DNA, the energy refined stereochemically satisfactory models provide valuable information which will hopefully simulate high resolution 2-D NMR/NOE studies in solution.
已对氨茴霉素与新型Z型十聚核苷酸d(GCGCGCGCGC)2和d(GCGCGTGCGC).d(GCGCACGCGC)之间的共价复合物进行了分子力学模拟，药物对接在小沟中。模拟预测氨茴霉素与Z-DNA的结合几乎与它与B-DNA的结合一样好，但在结合的结构方面存在一些关键差异。特别是，药物的5'方向在Z型中更受青睐，这与在B型中对3'方向的偏好形成对比，并且药物具有左手扭曲。虽然尚未发表关于吡咯并(1,4)苯并二氮杂卓与左手形式DNA结合的实验研究，但能量优化的立体化学满意模型提供了有价值的信息，有望模拟溶液中的高分辨率二维核磁共振/核Overhauser效应研究。
