Structure and conformation of saframycin R determined by high field 1H and 13C NMR and its interactions with DNA in solution.

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Abstract
The chemical structure and conformation of the new antitumor antibiotic saframycin R were determined by high field 1H and 13C NMR as well as FAB [fast atom bombardment] 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. Thus, saframycin R may be regarded as a less toxic prodrug for the active forms of saframycins A or S. [Calf thymus DNA, phage PM2 DNA and phage .lambda. DNA were used.].