DNA recognition by intercalators and hybrid molecules.

摘要: Experimental are described which probe the role of 2-amino group guanine as a critical determinant recognition nucleotide sequences in DNA by specific ligands. Homologous samples tyrT substituted with inosine or 26-diaminopourine residues place guanosine adenine respectively yield characteristically modified footprinting patterns when challenged sequence-selective antibiotics such echinomycin, actinomycin netrospin. The capacity small molecules to recognise particular is exploited ‘combilexin’ strategy target defined sites DNA. A composite molecule containing distamycin moiety linked an intercalating ellipticine derivative has been synthesised and shown bind tightly but without much sequence-selectivity. Refinement this based on predictions from molecular modelling led synthesis second generation bearing additional positive charge: new hybrid strongly selective for binding AT-rich tracts