title: Synthesis of [Ru(phen)(2)dppz](2+)-tethered oligo-DNA and studies on the metallointercalation mode into the DNA duplex.
abstract: To explore the binding properties of [Ru(phen)(2)dppz](2+) complex (phen = 1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine) in a sequence-specific manner in DNA duplex, it was tethered through the dppz ligand to a central position as well as both at the 3'- and 5'-ends of oligodeoxyribonucleotide (ODN). The middle [Ru(phen)(2)dppz](2+)-ODN tethered was resolved and isolated as four pure diastereomers, while the 3'- or 5'-[Ru(phen)(2)dppz](2+)-ODNs were inseparable on RP-HPLC. Thermal stability of the (Ru(2+)-ODN).DNA duplexes is found to increase considerably (DeltaT(m) = 12.8-23.4 degrees C), depending upon the site of the covalent attachment of the tethered [Ru(phen)(2)dppz](2+) complex, or the chirality of the [Ru(phen)(2)dppz](2+)-linker tethered at the middle of the ODN, compared to the unlabeled counterpart. Gross differences in CD between the [Ru(phen)(2)dppz](2+)-tethered and the native DNA duplexes showed that the global duplex conformation of the former has considerably altered from the B-type, but is still recognized by DNase I. The thermal melting studies, CD measurements, as well as DNase I digestion data, are interpreted as a result of intercalation of the dppz moiety, which is realized by threading of the Ru(phen)(2) complex part through the DNA duplex core. DNase I footprinting with four diastereomerically pure middle ([Ru(phen)(2)dppz](2+)-ODN).DNA duplexes furthermore showed that the tethered [Ru(phen)(2)dppz](2+)-linker chirality dictates the stereochemical accessibility of various phosphodiester moieties (around the intercalation site) toward the cleavage reaction by the enzyme. The diastereomerically pure ruthenium-modified duplexes, with the well-defined pi-stack, will be useful to explore stereochemistry-dependent energy- and electron-transfer chemistry to understand oxidative damage to the DNA double helix as well as the long-range energy- and electron-transfer processes with DNA as a reactant.
authors.affiliation: Department of Bioorganic Chemistry, Box 581, Biomedical Center, University of Uppsala, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Ossipov
authors.forename: P I
authors.initials: PI
authors.lastname: Pradeepkumar
authors.forename: M
authors.initials: M
authors.lastname: Holmer
authors.forename: J
authors.initials: J
authors.lastname: Chattopadhyaya
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D013696:Temperature
chemical_list: D009838:Oligodeoxyribonucleotides; D012313:RNA; D012428:Ruthenium; D004247:DNA; D003850:Deoxyribonuclease I