Studies on the mechanism of DNA sequence selective alkylation by kapurimycin A3 analogs.
We synthesized kapurimycin A3 ABCD-ring analog and compared the sequence selectivity for DNA guanine alkylation with those of kapurimycin A3 and ABC-ring analog. In the binding to DNA, it was shown by DNA unwinding assay that ABCD-ring analog binds tightly to DNA by intercalation into DNA duplex. DNA alkylation by ABCD-ring analog was sequence selective with an order of G*G > G*A > G*T > G*C. ABCD-ring analog has a stronger binding ability, a higher reactivity to DNA and a higher GG sequence selectivity in DNA alkylation than those to ABC-ring analog. The aromatic ring system plays an important role in the effective GG selective alkylation.
Okamoto
A
A
Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, Japan.
Nakatani
K
K
Saito
I
I
D000478:Alkylation; D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000873:Anthracenes; D000903:Antibiotics, Antineoplastic; D009838:Oligodeoxyribonucleotides; D011753:Pyrones; C066903:kapurimycin A3; D004247:DNA