Gao X, Stassinopoulos A, Gu J, Goldberg I H
Department of Chemistry, University of Houston, TX 77204-5641, USA.
Bioorg Med Chem. 1995 Jun;3(6):795-809. doi: 10.1016/0968-0896(95)00063-m.
The glutathione post-activated neocarzinostatin chromophore (NCSi-glu)-DNA complex was studied in detail by 2-D NMR spectroscopy. The complex is a model for understanding the sequence specific cleavage of DNA by the native neocarzinostatin chromophore (NCS chrom), a highly potent enediyne antitumor agent. NMR spectral analysis is presented for the free NCSi-glu, the free DNA duplex and the NCSi-glu-DNA complex. In addition to the previously reported structural details of the complex (Gao, X.; Stassinopoulos, A.; Rice, J. S.; Goldberg, I. H. Biochemistry 1995, 34, 40), we demonstrate that the binding of NCSi-glu in minor groove results in a patch of negatively charged surface covering the otherwise relatively neutral minor groove. The formation of the complex is largely driven by hydrophobic forces and the solvation of the polar surface of the complex. Comparison of the conformations of NCSi-glu and DNA duplex in their free and bound form reveals an induced mutual fit of DNA and NCSi-glu upon complex formation. The reduced NCS chrom represents a DNA binding motif for sequence specific recognition of DNA via intercalation and minor groove interactions.
通过二维核磁共振光谱对谷胱甘肽后活化的新制癌菌素发色团（NCSi - glu）-DNA复合物进行了详细研究。该复合物是理解天然新制癌菌素发色团（NCS chrom，一种高效的烯二炔抗肿瘤剂）对DNA进行序列特异性切割的模型。文中给出了游离NCSi - glu、游离DNA双链体以及NCSi - glu - DNA复合物的核磁共振光谱分析。除了之前报道的复合物结构细节（高，X.；斯塔西诺普洛斯，A.；赖斯，J. S.；戈德堡，I. H.《生物化学》1995年，34卷，40页），我们还证明NCSi - glu在小沟中的结合导致了一片带负电荷的表面覆盖原本相对中性的小沟。复合物的形成主要由疏水作用力以及复合物极性表面的溶剂化作用驱动。对NCSi - glu和DNA双链体在游离态和结合态的构象比较揭示了复合物形成时DNA和NCSi - glu之间的诱导相互适配。还原型NCS chrom代表了一种通过插入和小沟相互作用对DNA进行序列特异性识别的DNA结合基序。
