Binding of saframycin A, a heterocyclic quinone anti-tumor antibiotic to DNA as revealed by the use of the antibiotic labeled with [14C]tyrosine or [14C]cyanide.

Saframycin A is antitumor antibiotic structurally characterized by twin heterocyclic quinone skeletons and alpha-cyanoamine moiety. The binding of saframycin A to DNA was investigated using the antibiotic labeled at different positions. Heterocyclic quinone skeletons were biosynthetically labeled with [14C]tyrosine. The cyano residue of saframycin A was specifically labeled as a result of the reaction of [14C]cyanide with a derivative of saframycins, decyanosaframycin A, in the culture filtrate. When calf thymus DNA was incubated with [14C]tyrosine-labeled saframycin A in the presence of dithiothreitol, radioactivities were progressively recovered from DNA fraction. In contrast, saframycin A in the absence of dithiothreitol was completely devoid of reactivity toward DNA. When [14C]cyanide-labeled saframycin A was reacted with DNA, however, none of the radioactivity was associated with DNA. The release of cyano residue from the antibiotic was triggered by the reduction. Thus, conversion of quinone to hydroquinone skeletons as well as conversion of alpha-cyanoamine to immonium or alpha-carbinolamine is the consequence of the reduction. The fact that dithiothreitol-inducible binding of saframycin A to DNA was blocked by the addition of excess cyanide indicates that immonium or alpha-carbinolamine is the actual species involved in the interaction with DNA. The striking similarities between saframycin A and anthramycin in regard to the mode of binding to DNA are discussed.