Efficient guanine alkylation through cooperative heterodimeric formation of duocarmycin A and distamycin A

Abstract

Antitumor antibiotic Duocarmycin A alkylates adenines at the 3 end of sequences of three or more consecutive A or T base pairs through binding to the minor groove of DNA. In the presence of distamycin A, duocarmycin A was found to alkylate guanine residue in G-C rich sequences, which are not alkylated by duocarmycin A alone. Efficient guanine alkylation through cooperatively binding of a heterodimer in the minor groove of DNA will be discussed.