Site specific covalent alkylation of DNA by antitumor antibiotics, duocarmycin A and kapurimycin A3.
DNA alkylation by two different antitumor antibiotics, duocarmycin A and kapurimycin A3 was investigated by using of synthetic oligonucleotides. It was found that duocarmycin A reacted with N3 of adenine6 in d(CGTATACG)2 to provide a stable adduct. Kapurimycin A3 was found to react with d(CGCG)2 at N7 of guanine4 to yield a covalent adduct. Under heating conditions both adducts decompose to give an abasic-containing oligomer and a drug-base adduct.
Sugiyama
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Department of Synthetic Chemistry, Faculty of Engineering, Kyoto University, Japan.
Lam
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Hosoda
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Saito
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D000478:Alkylation; D000873:Anthracenes / Q000737:chemistry / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D000080890:Duocarmycins; D007211:Indoles; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology
D000873:Anthracenes; D000903:Antibiotics, Antineoplastic; D000080890:Duocarmycins; D007211:Indoles; D009838:Oligodeoxyribonucleotides; D011753:Pyrones; D011760:Pyrrolidinones; C066903:kapurimycin A3; D004247:DNA; C058289:duocarmycin A