新的手性铂络合物与DNA两种不同结合方式中的分子识别

Molecular recognition of two binding modes of DNA with novel chiral Pt complexes

深入探讨手性铂络合物与DNA作用的分子机制 ,寻找抗癌铂络合物的设计规律。方法 :用生物量热技术、DNATm测量、粘度滴定及NMR技术研究了手性不同的环方铂及环斑铂与CT DNA的作用。结果 :发现环方铂是通过方酸根的离去与DNA碱基之间形成共价键而结合的 ,而环斑铂是通过嵌插到DNA碱基对之间以非共价方式与DNA结合的。通过HPLC研究发现这两类铂络合物与DNA结合的碱基特异性完全不同。结论 :本研究发现铂络合物对DNA的识别作用是手性相关的 ,这与癌细胞体外筛选的结果一致。通过计算机分子图形学对以上实验结果从理论上进行了初步分析。

Objective: To study the molecular mechanism of the interaction between DNA and chiral Pt complexes. Methods: Two kinds of binding modes between DNA and the chiral isomers were evaluated by bio microcalorimetric techniques and DNA Tm measurements. The binding molecular mechanism of R,R SA Pt and DNA was investigated by 13 CNMR and DNA viscosity titrations. The binding specificity study of DNA base with the two kinds of novel Pt complexes was conducted by HPLC. Results: Covalent binding and noncovalent binding interaction were evaluated, and DNA binding specificity differences between R,R and S,S isomers were found. Conclusion: The effects of the chirality of the 1,2 diaminocyclohexane isomers and stereochemistry of the whole complexes on their anticancer activities and DNA molecular recognition have been discussed.