Sequence-specific recognition and cleavage of DNA by anti-tumour antibiotics |
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Authors: | Yukio Sugiura Le Luo Guan |
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Institution: | Institute for Chemical Research, Kyoto University , Uji, Kyoto, 611, Japan |
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Abstract: | Abstract DNA cleavage by a bleomycin—iron complex occurs preferentially at guanine-pyrimidine (5′ → 3′) sequences, in particular at G-C sites. Metallobleomycin binds in the minor groove of B-DNA and the bithiazole moiety probably plays an important role as an anchor on DNA duplex. The 2-amino group of guanine adjacent to the 5′-side of the cleaved pyrimidine base is one key element of the specific 5′-GC recognition by the bleomycin-metal complex. Endiyne anti-tumour antibiotics such as esperamicin A1 and dynemicin A also interact with the minor groove of DNA, and their strong DNA splitting activity is due to phenylene diradical formation from the enediyne core. A possible binding mode between these antibiotics and B-DNA has been proposed by computer-constructed model building. |
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