DNA minor groove recognition of a non-self-complementary AT-rich sequence by a tris-benzimidazole ligand

The crystal structure of the non-self-complementary dodecamer DNA duplex formed by d(CG[C-5Br]ATATTTGCG) and d(CGGAAATATGCG) has been solved to 2.3 Angstrom resolution, together with that of its complex with the tris-benzimidazole minor groove binding ligand TRIBIZ, The inclusion of a bromine atom on one strand in each structure enabled the possibility of disorder to be discounted, The native structure has an exceptional narrow minor groove, of 2.5-2.6 Angstrom in the central part of the A/T region, which is increased in width by similar to 0.8 Angstrom on drug binding. The ligand molecule binds in the central part of the sequence. The benzimidazole subunits of the ligand participate in six bifurcated hydrogen bonds with A:T base pair edges, three to each DNA strand. The presence of a pair of C-H...O hydrogen bonds has been deduced from the close proximity of the pyrrolidine group of the ligand to the TpA step in the sequence.