Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

摘要

With the goal of developing a better understanding of the antiparasitic biological action of 131375, we have evaluated its interaction with duplex alternating and nonaltemating sequence AT polymers and oligomers. These DNAs provide an important pair of sequences in a detailed thermodynamic analysis of variations in interaction of DB75 with AT sites. The results for DB75 binding to the alternating and nonalternating AT sequences are quite different at the fundamental thermodynamic level. Although the Gibbs energies are similar, the enthalpies for DB75 binding with poly(dA)-poly(dT) and poly(dA-dT)-poly(dA-dT) are +3.1 and -4.5 kcal/mol, respectively, while the binding entropies are 41.7 and 15.2 caUmol center dot K, respectively. The underlying thermodynamics of binding to AT sites in the minor groove plays a key role in the recognition process. It was also observed that DB75 binding with poly(dA)-poly(dT) can induce T-A-T triplet formation and the compound binds strongly to the dT-dA-dT triplex. (c) 2007 Elsevier B.V. All rights reserved.