顺铂与DNA键合机制的CNDO/2研究

本文用CNDO/2法研究了顺铂与DNA键合的机制.计算结果指出,在所考虑的几个模型配合物中,从Pt-N_7间重叠集居和双原子能分析,以顺铂与两个鸟嘌呤的N_7键合形成[(NH_3)_2PtG_2]~(2 )的可能性最大,因而支持了顺铂和DNA的相邻两个鸟嘌呤的N_7键合的链内交联机制.但是,螯合机理不能完全排除,在一定条件下,顺铂可能与一个鸟嘌呤的N_7和O键合形成一定量的螯合物.然而,由于它较[(NH_3)_2PtG_2]~(2 )不稳定,因此,不能成为顺铂伤害癌细胞的主要原因.至于链内交联机理如何造成DNA复制障碍尚待进一步研究.

A CNDO/2 study on bonding mechanism of cisplatin and DNA

Bonding mechanism of cisplatin with DNA has been studied by CNDO/2 calculation. The computed results of the six models considered indicated that form the point of view of overlap population QAB and two atoms energy EAB, the most favorable bonding from was that between cisplatin and two N7 atoms, each from one of the two guanines to form ((NH3)2PtG2)2+. Thus, intrastrand cross-linkage mechanism which had been proposed before by some authors was confirmed by our calculation. Chelation mechanism could not completely be excluded. Under certain conditions, it was possible for cisplatin to combine with a guanine through its N7 and O to form a chelate, but it was unstable as compared with((NH3)2PtG2)2+. Although the intrastrand cross-linkage mechanism is favored by our calculation, the way such a mode of combination hampers replication of DNA remains to be solved.