Synthesis and DNA binding properties of 1-(3-aminopropyl)-imidazole-containing triamide f-Im∗PyIm: A novel diamino polyamide designed to target 5′-ACGCGT-3′

A novel diamino/dicationic polyamide f-Im∗PyIm (5) that contains an orthogonally positioned aminopropyl chain on an imidazole (Im∗) moiety was designed to target 5′-ACGCGT-3′. The DNA binding properties of the diamino polyamide 5, determined by CD, ΔTM, DNase I footprinting, SPR, and ITC studies, were compared with those of its monoamino/monocationic counterpart f-ImPyIm (1) and its diamino/dicationic isomer f-ImPy∗Im (2), which has the aminopropyl group attached to the central pyrrole unit (Py∗). The results gave evidence for the minor groove binding and selectivity of polyamide 5 for the cognate sequence 5′-ACGCGT-3′, and with strong affinity (Keq = 2.3 × 107 M−1). However, the binding affinities varied according to the order: f-ImPy∗Im (2) > f-ImPyIm (1) ⩾ f-Im∗PyIm (5) confirming that the second amino group can improve affinity, but its position within the polyamide can affect affinity.