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.
Uesawa
Y
Y
Institute for Chemical Research, Kyoto University, Japan.
Sugiura
Y
Y
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D053281:Enediynes; D006358:Hot Temperature; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010957:Plasmids
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D004247:DNA; C047543:esperamicin A1