Design, synthesis and DNA binding properties of orthogonally positioned diamino containing polyamide f-IPI.

An orthogonally positioned diamino/dicationic polyamide f-IPI 2 was synthesized. It has enhanced binding affinity, and it showed comparable sequence specificity to its monoamino/monocationic counterpart f-IPI 1. Results from CD and DNase I footprinting studies confirmed the minor groove binding and selectivity of polyamides 1 and 2 for the cognate sequence 5'-ACGCGT-3'. SPR studies provided their binding constants: 2.4 × 10(8)M(-1) for diamino 2, which is ∼4 times higher than 5.4 × 10(7)M(-1) for its monoamino analogue 1.