| Abstract
| - The source of hydrogens for the quenching of the phenylenediradical produced by esperamicin A (espA)and by esperamicin C (espC) in the presence of specificallydeuteriated, double-stranded DNA (dsDNA) has beendetermined. Remarkably, both espA and espC were quenched at bothpositions of the diphenylene radical by exclusiveabstraction of hydrogen from dsDNA. EspC, a predominantlyds-cleaver, afforded results consistent with 4‘- and5‘-hydrogen transfer. EspA, a predominantly ss-cleaver, revealedno 4‘-hydrogen transfer; however, results wereconsistent with 5‘-hydrogen transfer and with the recently proposed1‘-hydrogen transfer (Yu, L.; Golik, J.; Harrison,R.; Dedon, P. J. Am. Chem. Soc. 1994,116, 9733−9738). For espA, insufficient double strandDNA damage wasproduced to account for the role of DNA as the exclusive hydrogensource. In order to resolve this discrepancy,several reductants were used to activate espA and espC. Theresults indicated that a substantial portion of radicallesions produced in DNA by the esperamicins is subjected to repair byhydrogen transfer from the reductant. Theefficiency of repair depended on the structural features of thereductant. The findings demonstrate that caution mustbe exercised when evaluating the propensity of DNA cleavers for ss- andds-cleavage in the presence of reductants.
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