ONIOM Study on the DNA Interstrand Crosslinks by the Chloroethylnitrosoureas
Chloroethylnitrosoureas (CENUs) are clinically useful anticancer agents. Their cytotoxicity has been proved to be associated with the generation of DNA interstrand crosslinks. In the present work, QM/MM computations are carried out to investigate the crosslinks of DNA complementary bases by the CENUs with ONIOM hybrid method. DNA double helix containing crosslinked base pairs are established as the computational models. The crosslinked DNA are subdivided into three layers, each of which are described at B3LYP/6-311+G(d,p), AM1 and UFF level of theory respectively. The result shows that the covalent crosslink between guanine N1 and complementary cytosine N3 is the most favorable crosslinking product. This crosslink is characterized by its less deformation of DNA double helix and higher stability than the other crosslinks on the complementary base pairs. The results of the ONIOM computations explain the phenomenon that 1-(N3-deoxycytidyl)-2-(N1-deoxyguanosinyl)ethane is the main crosslink product in the in vivo an the in vitro experiments.
Chloroethylnitrosoureas Crosslink ONIOM
Li-Jiao Zhao Ru-Gang Zhong Yan Zhen
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100022, China
国际会议
北京
英文
257-260
2007-05-23（万方平台首次上网日期，不代表论文的发表时间）