A noncovalent binding-translocation mechanism for site-specific CC-1065-DNA recognition

作者: Daniela Gunz , Hanspeter Naegeli

DOI: 10.1016/0006-2952(96)00247-X

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摘要: Abstract The molecular strategy by which small organic compounds recognise specific DNA sequences is of primary importance for rational drug design. CC-1065 a potent alkylating agent that binds covalently to N3 adenine and lies in the minor groove double-stranded DNA. Its reaction with occurs site-specific manner, preference A · T-rich nucleotide sequences. In present study, we developed translocation assay investigate mechanism underlying this sequence selectivity. After exposure plasmid saturating amounts CC-1065, observed nearly 70% plasmid-bound molecules formed stable, but noncovalent, complexes These noncovalently bound resisted purification ethanol precipitation, dialysis, sucrose gradient centrifugation, retained ability translocate fragments containing single high-affinity site alkylation. This combination noncovalent binding interactions provides may locate alkylation sites

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