title: Genistein binding mode to doubly nicked dumbbell DNA. Dynamic and diffusion ordered NMR study.
abstract: New genistein derivatives were synthesized, which are fairly well soluble in water, with respect to parent genistein, and thus facilitate study of the interaction with dumbbell DNA dodecamer, mimicking the biological target for topoisomerase II inhibitors. A pulsed field gradient spin echo NMR experiment was used to check the binding and to estimate the association constants and its pH dependence of genistein with dumbbell DNA. Experimental restraints based on nuclear Overhauser spectroscopy spectra were used to calculate the NMR structure in solution in case of 6,8-disubstituted genistein with dimethylaminomethyl groups and were used in molecular modeling calculations. The structure is dynamic, and 10 molecular dynamics runs yield a family of conformations that essentially differ in a depth of inclusion of genistein into a nick. The paper experimentally shows evidence for binding, intercalation in the nick is proposed as a mode of genistein binding, and a model of the event is provided.
authors: Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warszawa, Kasprzaka 44, Poland.
authors: Karolina
authors: K
authors: Hyz
authors: Robert
authors: R
authors: Kawęcki
authors: Aleksandra
authors: A
authors: Misior
authors: Wojciech
authors: W
authors: Bocian
authors: Elżbieta
authors: E
authors: Bednarek
authors: Jerzy
authors: J
authors: Sitkowski
authors: Lech
authors: L
authors: Kozerski
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D019833:Genistein / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D012996:Solutions; D013936:Thymidine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D009841:Oligonucleotides; D012996:Solutions; D004247:DNA; D019833:Genistein; D013936:Thymidine