Imidazopyridine/pyrrole and hydroxybenzimidazole/pyrrole pairs for DNA minor groove recognition

The DNA binding properties of fused heterocycles imidazo[4,5-b]pyridine (1p) and hydroxybenzimidazole (Hz) paired with pyrrole (Py) in eight-ring hairpin polyamides are reported. The recognition profile of Ip/Py and Hz/Py pairs were compared to the five-membered ring pairs Im/Py and Hp/Py on a DNA restriction fragment at four 6-base pair recognition sites which vary at a single position 5'-TGTNTA-3', where N = G, C, T, A. The Ip/Py pair distinguishes G-C from C-G, T-A, and A-T, and the Hz/Py pair distinguishes T-A from A-T, G-C, and C-G, affording a new set of heterocycle pairs to target the four Watson-Crick base pairs in the minor groove of DNA.