title: Hydroxyl radical generation by oligonucleotide derivatives of anthracycline antibiotic and synthetic quinone.
abstract: For the first time the covalent binding of anticancer anthracycline drugs and their potential synthetic analogs to oligonucleotides of different sequences is proposed for obtaining site-specific DNA scission in systems in vitro and in vivo. New compounds such as daunomycin (Dm) and synthetic naphthoquinone (NQ), covalently bound to the heptadeoxynucleotide of pCCAAACA (Dm-pN7) and decadeoxythymidilate (pT10p-NQ), have been obtained. These oligonucleotide derivatives can form specific complexes with complementary oligonucleotide sequences; these compounds and their complementary complexes can be reduced by purified NADPH-cytochrome P-450 reductase. Using the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), it has been shown that in aerobic conditions Dm-pN7 and pT10p-NQ are capable of generating OH radicals with and without complementary oligonucleotides. The chemical stability of the compounds in redox reactions has been studied. Oligonucleotide derivatives of natural and synthetic quinones capable of generating OH radicals seem to be a promising tool for site-specific scission of DNA in solution and in cells.
authors.affiliation: Institute of Chemical Kinetics and Combustion, Novosibirsk, U.S.S.R.
authors.forename: S I
authors.initials: SI
authors.lastname: Dikalov
authors.forename: G V
authors.initials: GV
authors.lastname: Rumyantseva
authors.forename: L M
authors.initials: LM
authors.lastname: Weiner
authors.forename: D S
authors.initials: DS
authors.lastname: Sergejev
authors.forename: E I
authors.initials: EI
authors.lastname: Frolova
authors.forename: T S
authors.initials: TS
authors.lastname: Godovikova
authors.forename: V F
authors.initials: VF
authors.lastname: Zarytova
mesh_terms: D001483:Base Sequence; D003497:Cyclic N-Oxides; D003630:Daunorubicin / Q000737:chemistry / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism*; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D006878:Hydroxides; D009285:Naphthoquinones; D009841:Oligonucleotides; D013113:Spin Labels; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D009251:NADPH-Ferrihemoprotein Reductase; D003630:Daunorubicin