UNMASKING THE CHEMISTRY OF DNA CLEAVAGE BY THE ESPERAMICINS - MODULATION OF 4'-HYDROGEN ABSTRACTION AND BISTRANDED DAMAGE BY THE FUCOSE ANTHRANILATE MOIETY

The chemistry of DNA cleavage by the esperamicins A1, C, D, and E (esp A, C-E) has been examined. High-resolution gel electrophoresis reveals that esp A, a known single-strand cleaver, affords fragmentation products consistent with exclusive 5'-hydrogen abstraction. In contrast, esp C-E, analogs that produce significant double-strand cleavage, generate fragmentation products consistent with both 5'- and 4'-hydrogen abstraction. On the basis of these observations and other findings reported for a related enediyne antibiotic, calicheamicin gamma1I (Townsend, C. A.; DeVoss, J. J.; Ding, W.-D.; Morton, G. O.; Ellestad, G. A.; Zein, N.; Tabor, A. B.; Schreiber, S. L. J. Am. Chem. Soc. 1990, 112, 9669), we conclude that 4'-hydrogen abstraction and bistranded DNA cleavage are directly related to the reactivity of the C-7 radical as modulated by the fucosyl-anthranilate group.