The molecular recognition mechanism of DNA by bleomycin.
The interaction between the antibiotic bleomycin (BLM) and an oligonucleotide d(CCACCTAGGTGG) was studied by 1H NMR. The DNA oligomer was titrated with BLM-VO(III), which is an 'inactive analogue' of BLM-Fe(II). A marked upfield shift was observed for the T10N3H signal, but no other imino proton signals either shifted or broadened. When BLM-VO(III) was titrated with d(CCACCTAGGTGG), a large upfield shift (0.27 ppm) was observed for the delta NH signal of butylguanidinium residue (G). Analysis of NOESY spectra of a 1:1 complex of DNA:BLM-VO(III) strongly suggests that the connectivities of the sequential NOEs of the DNA duplex are the same as those of free DNA. These results indicate that BLM does not intercalate between the base-pairs but binds to DNA in a different manner. A model of 'minor-groove binding' is more likely to explain our NMR data.
Hiroaki
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H
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Uesugi
S
S
Fujii
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D001483:Base Sequence; D001665:Binding Sites; D001761:Bleomycin / Q000737:chemistry*; D002240:Carbohydrate Sequence; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
D009838:Oligodeoxyribonucleotides; D001761:Bleomycin; D004247:DNA