SPONTANEOUS GENERATION OF A BIRADICAL SPECIES OF NEOCARZINOSTATIN CHROMOPHORE - ROLE IN DNA BULGE-SPECIFIC CLEAVAGE

Detailed structure determination of the major and minor base-catalyzed degradation products of the chromophore of the enediyne anticancer an tibiotic neocarzinostatin in the absence of DNA demonstrates that the enolate Michael addition reaction leading to a spirolactone cumulene i ntermediate is a spontaneous, stereoselective process. The implication s of these findings for the mechanism of the thiol-independent, site-s pecific cleavage by the so-generated radical species of the drug at a DNA bulge are described.