Tc. Jenkins et al., NMR AND MOLECULAR MODELING STUDIES OF THE INTERACTION OF BERENIL AND PENTAMIDINE WITH D(CGCAAATTTGCG)2, European journal of biochemistry, 213(3), 1993, pp. 1175-1184
The interaction of two anti-trypanosomal agents, berenil and pentamidi
ne, with the A+T-rich dodecamer d(CGCAAATTTGCG)2 has been examined by
high-resolution H-1-NMR. optical spectroscopy, and molecular modeling.
Proton assignments for the free DNA and each DNA-ligand complex were
obtained using nuclear Overhauser enhancement spectroscopy and total c
orrelation spectroscopy. Complexation induces large changes in chemica
l shift for protons in the DNA minor groove for the A5-T9 segment, and
intermolecular NOEs reveal contacts between the DNA bases and each li
gand. The asymmetric binding site for berenil indicated by the NMR dat
a suggests that at least two overlapping sites are involved. Rapid exc
hange between symmetrically-equivalent binding sites, via dissociative
rearrangement, is consistent with retention of twofold degeneracy for
both the ligand and the DNA host. Calculations of binding energy conf
irm that this DNA duplex contains overlapping sites of similar binding
affinity. In contrast, the larger pentamidine molecule occupies a sit
e that spans four or five bp, with asymmetric binding to the minor-gro
ove 5'-ATTT sequence. The B-type conformation of the DNA is not altere
d substantially by either ligand.