刺孢霉素γ1与pBR322 DNA片段相互作用的模型

Hawley R C, Kiessling L L, Schreiber S L

Department of Chemistry, Yale University, New Haven, CT 06511.

Proc Natl Acad Sci U S A. 1989 Feb;86(4):1105-9. doi: 10.1073/pnas.86.4.1105.

An analysis of the binding interactions of several DNA-drug complexes that utilize carbohydrates for DNA recognition has been undertaken. It is proposed that the carbohydrate residues function as general minor groove binding elements, and the stereochemistry of aglycone attachment sites is generally disposed to promote a right-handed helical geometry that is complementary to right-handed DNA. The constitution and stereochemistry of the DNA double-strand cleaving agent calichemicin gamma 1 is consistent with this analysis. Docking experiments with computer-generated models of this drug and a dodecamer duplex that was found to serve as a calichemicin cleavage site were performed to gain insight into the origin of the drug's sequence-selective binding and cutting properties. A model is presented that provides a molecular level understanding of the double-strand cleavage patterns that result from the action of calichemicin gamma 1 on DNA.

已对几种利用碳水化合物识别DNA的DNA-药物复合物的结合相互作用进行了分析。有人提出，碳水化合物残基作为一般的小沟结合元件发挥作用，糖苷配基连接位点的立体化学通常倾向于促进与右手DNA互补的右手螺旋几何结构。DNA双链切割剂刺孢霉素γ1的组成和立体化学与该分析一致。对该药物的计算机生成模型和被发现用作刺孢霉素切割位点的十二聚体双链体进行对接实验，以深入了解药物的序列选择性结合和切割特性的起源。提出了一个模型，该模型从分子水平上解释了刺孢霉素γ1作用于DNA所产生的双链切割模式。