A 1H NMR analysis of the interaction between terephthalamide derivatives and the oligonucleotide duplex...

A series of terephthalamide derivatives with the substituents R = NO2, NH2 and NHCOCH2NH2 on the central aryl ring have been synthesized, and their interaction with the DNA decamer d(GGTAATTACC)2 has been studied by 1H NMR. The amine and nitro (R = NH2, NO2) derivatives bind with micromolar affinities and exhibit NMR spectra characteristic of fast exchange on the chemical shift time scale. The glycine derivative (R = NHCOCH2NH2) binds more tightly and a number of its resonances are in intermediate to slow exchange on the chemical shift time scale. Estimates of binding affinities and bound chemical shifts of ligand and DNA resonances were made from an analysis of chemical shifts and linewidths in a series of spectra with ligand duplex mole ratios ranging from 0:1 to 2:1. The data unequivocally suggest that all three ligands bind in the minor groove of the DNA decamer and more specifically that the binding site is localized over the ATTA sequence. The ligand is able to exchange rapidly between two symmetry-related ATTA sites per decamer.