Expanding the Repertoire of Heterocycle Ring Pairs for Programmable Minor Groove DNA Recognition The text of this chapter was taken in part from a manuscript coauthored with Raymond

Abstract. The discrimination of the four Watson-Crick base pairs by minor groove DNA binding polyamides have been attributed to the specificity of three 5-membered aromatic amino acid subunits, 1-methyl-1H-imidazole (Im), 1-methyl-1H-pyrrole (Py), and 3-hydroxy-1H-pyrrole (Hp) paired four different ways. The search for additional ring pairs that demonstrate DNA sequence specificity has led us to a new class of 6-5 fused bicycle rings as minor groove recognition elements. The affinities and specificities of the hydroxybenzimidazole/pyrrole (Hz/Py) and hydroxybenzimidazole/benzimidazole (Hz/Bi) pairs for each of the respective Watson-Crick base pairs within the sequence context 5’-TGGXCA-3 ’ (X = A, T, G, C) were measured by quantitative DNase I footprinting titrations. The Hz/Py and Hz/Bi distinguish T●A from A●T. Hairpin polyamides containing multiple Hz/Py pairs were examined and shown to mimic the Hp/Py pair with regard to affinity and specificity. Therefore the Hz/Py pair may b