STRUCTURE AND CONFORMATION OF SAFRAMYCIN R DETERMINED BY HIGH FIELD ¹H AND ¹³C NMR AND ITS INTERACTIONS WITH DNA IN SOLUTION

Abstract

The chemical structure and conformation of the new antitumor antibiotic saframycin R have been determined by high field ¹H and ¹³C NMR as well as FAB mass spectrometry. Unlike other members of the saframycin family, saframycin R contains a reduced quinone ring bearing a glycolic ester moiety. Saframycin R exhibits acid promoted equilibrium and reversible covalent binding to DNA templates and, in the presence of a reducing agent, oxygen dependent single strand scission of supercoiled DNA. The extent of DNA scission is enhanced by in situ porcine carboxyl esterase or base catalyzed cleavage of the glycolic ester function plausibly by the release of the more reactive reduced saframycin A. This suggests that saframycin R may be regarded as a less toxic pro-drug for the active forms of saframycins A or S.