Binding of bis-linked netropsin derivatives in the parallel-stranded hairpin form to DNA

Cis-diammine Pt(II)- bridged bis-netropsin and oligomethylene-bridged bis-n etropsin in which two monomers are linked in a tail-to-tail manner bind to the DNA oligomer with the sequence 5'-CCTATATCC-3' in a parallel-stranded h airpin form with a stoichiometry 1:I. The difference circular dichroism (CD ) spectra characteristic of binding of these ligands in the hairpin form ar e similar. They differ from CD patterns obtained for binding to the same du plex of another bis-netropsin in which two netropsin moieties were linked i n a head-to-tail manner. This reflects the fact that tail-to-tail and head- to-tail bis-netropsins use parallel and antiparallel side-by-side motifs, r espectively, for binding to DNA in the hairpin forms. The binding affinity of cis-diammine Pt(II)- bridged bis-netropsin in the hairpin form to DNA ol igomers with nucleotide sequences 5'-CCTATATCC-3' (I), 5'-CCTTAATCC-3' (II) , 5'-CCTTATTCC-3' (III), 5'-CCTTTTTCC-3' (IV) and 5'-CCAATTTCC-3' (V) decre ases in the order I = II > III > IV > V. The binding of oligomethylene-brid ged bis-netropsin in the hairpin form follows a similar hierarchy. An oppos ite order of sequence preferences is observed for partially bonded monodent ate binding mode of the synthetic ligand.