Hebei Key Laboratory of Heterocyclic Compounds, College of Chemistry, Chemical Engineering and Materials, Handan University, Handan, 056005 Hebei province, China.
College of Chemistry, Beijing Normal University, 19# Xinjiekouwai Street, Beijing 100875, China.
J Chem Inf Model. 2020 Mar 23;60(3):1700-1708. doi: 10.1021/acs.jcim.0c00002. Epub 2020 Mar 4.
The monofunctional trinuclear platinum complex (MTPC), as a promising antitumor agent, can form MTPC-DNA adducts via bifunctional and trifunctional cross-links. Molecular dynamics simulations were used to investigate DNA structural distortions of the MTPC-DNA adducts. MTPC coordinating to DNA results in the decrease of base-pair thermal stability and DNA structural distortions. It is found that there are more significant DNA structural distortions in the trifunctional cross-link than in the bifunctional cross-link, in the 1,4-GG than in the 1,3-GG cross-link, and in the intrastrand than in the interstrand cross-link with the same spans. The results provide a better understanding of DNA structural distortions induced by MTPC with various cross-links at the nucleotide level and are helpful for exploring novel Pt-based anticancer drugs.
单核三核铂配合物（MTPC）作为一种很有前途的抗肿瘤药物，能够通过双功能和三功能交联形成 MTPC-DNA 加合物。采用分子动力学模拟研究了 MTPC-DNA 加合物的 DNA 结构扭曲。MTPC 与 DNA 配位导致碱基对热稳定性降低和 DNA 结构扭曲。结果发现，三功能交联比双功能交联、1,4-GG 比 1,3-GG 交联以及相同跨度的链内交联具有更大的 DNA 结构扭曲。这些结果从核苷酸水平更好地理解了不同交联形式的 MTPC 引起的 DNA 结构扭曲，有助于探索新型基于铂的抗癌药物。
