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 × 108 M−1 for diamino 2, which is ∼4 times higher than 5.4 × 107 M−1 for its monoamino analogue 1.

Research highlights
► A novel pyrrole and imidazole-containing polyamide, diamino f-IPI, is synthesized.
► Diamino f-IPI binds four times more strongly to 5′-ACGCGT-3′ than monoamino f-IPI.
► It binds 5′-ACGCGT-3′ with similar sequence selectivity as monoamino f-IPI.
► Second amino group in diamino f-IPI enhances water solubility.
► It also provides a nucleophilic site for modifications.