Products of DNA cleavage by the 1,10-phenanthroline-copper complex. Inhibitors of Escherichia coli DNA polymerase I.

Chemical nucleases

“…The following stable reaction products were identified: S'-phosphorylated termini, 3'-phosphorylated termini, free bases, and 5-methylenefuranone, as well as minor amounts of 3'-phosphoglycolate termini (Pope et al, 1982;Kuwabara et al, 1986;Goyne & Sigman, 1987). Since exonuclease III and alkaline phosphatase relieved the inhibition of E. coli Pol I by OP-Cu (Pope et al, 1982), 3'-phosphorylated termini are responsible for the observed inhibition of E. coli DNA polymerase I (and presumably all other polymerases) by 1,10phenanthroline. Earlier work had shown that the 3'phosphorylated ends produced by micrococcal nuclease digestion were inhibitors of Pol I (Englund et al, 1969).…”

Highly specific oxidative damage of double-strand DNA by copper aminoglycosides

“…Fe-bleomycin mediated cleavage shows evidence of both a major C-4AH cleavage path and for C-1AH abstraction. 2,3 While copper phenanthroline and copper desferal had previously been assigned a major C-1AH cleavage path, [4][5][6][7][8] more recent work has indicated that C-4AH and C-5AH abstractions are the only routes that lead to backbone scission. 9 Enediynes, oxochromium reagents and manganese porphyrin derivatives have also been shown to mediate C-1AH, C-4AH, and C-5AH abstraction.…”

Chemical Mechanism of DNA Scission by (1,10-Phenanthroline)copper. Carbonyl Oxygen of 5-Methylenefuranone Is Derived from Water

“…The tetrahedral 2:1 (1,10-phenanthroline)copper(I) complex ((OP) 2 Cu + ), cleaves the phosphodiester backbone of B-DNA under physiological conditions by oxidation of the deoxyribose moiety using hydrogen peroxide as an essential coreactant (eq 1). , The principal products are free base, 5-methylenefuranone (5-MF), and 3‘- and 5‘-phosphorylated ends (eq 2) . In this paper, we investigate the atom source of the carbonyl oxygen of 5-MF to elucidate the mechanism of this efficient nucleolytic activity.…”

“…In addition to the different source of oxygen of the carbonyl group of 5-MF, the reactions of (1,10-phenanthroline)copper and the manganese porphyrin with DNA also differ because the latter chelate reacts with guanosine of DNA when tethered to an oligonucleotide, generating alkaline labile sites which require piperidine treatment for strand scission . In contrast, the reaction of (1,10-phenanthroline)copper with the deoxyribose moiety of DNA leads to strand scission without the requirement of either alkaline or heat treatment. , …”