Efficient guanine alkylation through cooperative heterodimeric formation of duocarmycin A and distamycin A.
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.
Isomura
M
M
Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, Japan.
Sugiyama
H
H
Saito
I
I
D000478:Alkylation; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D019281:Dimerization; D004214:Distamycins / Q000737:chemistry* / Q000494:pharmacology; D000080890:Duocarmycins; D006147:Guanine / Q000737:chemistry*; D066298:In Vitro Techniques; D007211:Indoles; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D004214:Distamycins; D000080890:Duocarmycins; D007211:Indoles; D009838:Oligodeoxyribonucleotides; D011760:Pyrrolidinones; D006147:Guanine; C030000:stallimycin; D004247:DNA; C058289:duocarmycin A