Heat-induced DNA cleavage by esperamicin antitumor antibiotics

Esperamicin A1 effectively breaks DNA strands upon heating at 50 degrees C. The preferential DNA cutting sites of heat-activated esperamicin A1 are random and clearly differ from those of thiol- or UV-light-mediated DNA breakage with esperamicin A1. The absence of heat-induced DNA cleavage by esperamicin Z and the induction of the DNA breakage by esperamicin A1 disulfide indicate that (1) the enediyne core plays a significant role in this DNA strand scission and (2) the DNA cutting with the heat-activated esperamicin antibiotics does not necessarily require a trisulfide trigger in the aglycon portion. On the basis of the present results, a probable mechanism for the heat-induced DNA cleavage of esperamicin A1 has been proposed.