Hydroxyl radical generation by oligonucleotide derivatives of anthracycline antibiotic and synthetic quinone.

Dikalov SI, Rumyantseva GV, Weiner LM, Sergejev DS, Frolova EI, Godovikova TS, Zarytova VF
Chem Biol Interact. 1991 77 (3): 325-39

PMID: 1849049 · DOI:10.1016/0009-2797(91)90041-5

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.

MeSH Terms (13)

Base Sequence Cyclic N-Oxides Daunorubicin Electron Spin Resonance Spectroscopy Hydroxides Hydroxyl Radical Magnetic Resonance Spectroscopy Molecular Sequence Data Molecular Structure NADPH-Ferrihemoprotein Reductase Naphthoquinones Oligonucleotides Spin Labels

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