(ImHpPyPy)2 • AGTACT

X-ray crystal structure of the polyamide ImHpPyPy-β-Dp bound as a homodimer in the minor groove to the target DNA sequence, 5'-AGTACT-3'. Imidazole (Im), 3-hydroxypyrrole (Hp), and pyrrole (Py) residues are shown in red, yellow, and white, respectively. This structure demonstrates the complete set of pairing rules for specific recognition of all four Watson-Crick base pairs by Im/Hp/Py polyamides. Im/Py ring pairings target G·C base pairs via a directional hydrogen bond between the N-3 of Im and exocyclic amine of G. T·A vs A·T discrimination is achieved by Hp/Py and Py/Hp pairs, respectively. The 3-hydroxy of the Hp residue makes a hydrogen bond to the O-2 carbonyl of T and provides steric bulk that favors the asymmetric cleft on the T side of a T·A base pair. Further details of the structure can be found in Kielkopf et. al. and an overview of polyamide:DNA recognition is also provided.