DNA binding and cleavage by enediyne antitumor antibiotics, esperamicin and dynemicin.
Esperamicin A1 and dynemicin represent a new class of DNA binding/damaging agents characterized by unique ten-membered ene-diyne core. The former antitumor antibiotic shows high DNA cleavage activity in the presence of dithiothreitol, whereas the latter in the presence of NADPH. Esperamicin A1 favorably breaks T and C bases at oligopyrimidine regions such as 5'-CTC, 5'-TTC, and 5'-TTT sequences. Dynemicin attacks the bases at 3'-side of purine residues such as 5'-AG, 5'-AT, and 5'-GC sequences. These drugs also present good circumstantial evidence for minor groove interaction of B-DNA.
Shiraki
T
T
Institute for Chemical Research, Kyoto University, Japan.
Sugiura
Y
Y
D000617:Aminoglycosides; D000880:Anthraquinones / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D053281:Enediynes
D000617:Aminoglycosides; D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D004247:DNA; C061229:dynemicin A; C047543:esperamicin A1