title: Differences in conformational dynamics of [Pt3(HPTAB)]6+-DNA adducts with various cross-linking modes.
abstract: We present here molecular dynamics simulations and DNA conformational dynamics for a series of trinuclear platinum [Pt(3)(HPTAB)](6+)-DNA adducts [HPTAB = N,N,N',N',N'',N''-hexakis (2-pyridyl-methyl)-1,3,5-tris(aminomethyl) benzene], including three types of bifunctional crosslinks and four types of trifunctional crosslinks. Our simulation results reveal that binding of the trinuclear platinum compound to a DNA duplex induces the duplex unwinding in the vicinity of the platination sites, and causes the DNA to bend toward the major groove. As a consequence, this produces a DNA molecule whose minor groove is more widened and shallow compared to that of an undamaged bare-DNA molecule. Notably, for trifunctional crosslinks, we have observed extensive DNA conformational distortions, which is rarely seen for normal platinum-DNA adducts. Our findings, in this study, thus provide further support for the idea that platinum compounds with trifunctional intra-strand or long-range-inter-strand cross-linking modes can generate larger DNA conformational distortions than other types of cross-linking modes.
authors: College of Chemistry, Beijing Normal University, Beijing 100875, P R China.
authors: Yanyan
authors: Y
authors: Zhu
authors: Yan
authors: Y
authors: Wang
authors: Guangju
authors: G
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D020029:Base Pairing; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry*; D025341:Principal Component Analysis
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D009944:Organoplatinum Compounds