title: Interaction between double helix DNA fragments and a new topopyrone acting as human topoisomerase I poison.
abstract: A water soluble derivative (2) of topopyrones was selected for NMR studies directed to elucidate the mode of binding with specific oligonucleotides. Topopyrone 2 can intercalate into the CG base pairs, but the residence time into the double helix is very short and a fast chemical exchange averaging occurs at room temperature between the free and bound species. The equilibria involved become slow below room temperature, thus allowing to measure a mean lifetime of the complex of ca. 7 ms at 15 degrees C. Structural models of the complex with d(CGTACG)(2) were developed on the basis of DOSY, 2D NOESY and (31)P NMR experiments. Topopyrone 2 presents a strong tendency to self-associate. In the presence of oligonucleotide a certain number of ligand molecules are found to externally stack to the double-helix, in addition to a small fraction of the same ligand intercalated. The external binding to the ionic surface of the phosphoribose chains may thus represents the first step of the intercalation process.
authors.affiliation: Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, via Celoria 2, 20133 Milano, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Scaglioni
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazzini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mondelli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dallavalle
authors.forename: Sonia
authors.initials: S
authors.lastname: Gattinoni
authors.forename: Stella
authors.initials: S
authors.lastname: Tinelli
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Beretta
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Enzio
authors.initials: E
authors.lastname: Ragg
mesh_terms: D000880:Anthraquinones / Q000737:chemistry* / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D059004:Topoisomerase I Inhibitors
chemical_list: D000880:Anthraquinones; D007364:Intercalating Agents; D011753:Pyrones; D059004:Topoisomerase I Inhibitors; D004247:DNA