A New Imidazole-derivatized Diamino Polyamide Design: Synthesis and DNA Binding

Polyamides that are analogs of the natural product distamycin have proven to be effective agents to selectively bind in the minor groove of DNA. Of particular interest is the triamide containing imidazole and pyrrole heterocycles, f-ImPyIm, which showed better affinity and specificity in targeting its cognate DNA sequence, 5’-ACGCGT-3’ than distamycin’s preference for 5’-AAATTT-3’. Several analogues have been synthesized with different modifications, which alter properties such as solubility, fluorescence, binding affinity, and sequence specificity. It has been found that by placing a second amino group in a pyrrole unit of the polyamide core it is possible to improve binding affinity without compromising sequence selectivity. Such an amino group helps to increase solubility of polyamides in aqueous media. In this project a novel polyamide containing a comparably functionalized imidazole ring was synthesized to study it’s DNA recognition properties