76(P62) DNAにインターカレーションするアルキル化剤のグアニン-グアニン配列選択的DNAアルキル化(ポスター発表の部)

概要

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There are a lot of small molecules which can selectively modify DNA at guanine (G) base. Aflatoxin B_1 and psorospermin are a member of these molecules and have characteristic structure that consists of a plane aromatic ring system and an epoxide subunit alkylating G-N7. G alkylation by these drugs is sequence selective with preference of 3'-G in 5'-GG-3' step. We have previously reported that kapurimycin A_3, a member of pluramycin antibiotics, and its ABC ring analog efficiently alkylate DNA with high preference of 5'-G in 5'-GG-3' step. In order to investigate the difference of sequence selectivity between kapurimycins and aflatoxins, we have carried out DNA unwinding of supercoiled DNA, and DNA cleaving experiments of duplex DNA oligomer by ABC and ABCD' ring analogs of kapurimycin. The results of these experiments clearly indicated that ABC and ABCD' ring analog of kapurimycin A_3 intercalate DNA and alkylate the the 5' side G at the intercalation site. We have also examined the DNA alkylation by enantiomer of ABCD' ring analog, and found very low reactivity and selectivity for G alkylation. Based on these data, we proposed that neutral DNA alkylating agents having a plan aromatic ring system tend to intercalate between two G's in 5'-GG-3' step and the G selectivity in the sequence could be primarily determined by olientational necessary for S_N2 reaction between G-N7 and epoxide.
天然有機化合物討論会の論文
1997-07-20