Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove.
With the goal of developing a better understanding of the antiparasitic biological action of DB75, we have evaluated its interaction with duplex alternating and nonalternating 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 cal/mol.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.
Liu
Yang
Y
Department of Chemistry, Georgia State University, Atlanta, GA 30302-4098, USA.
Kumar
Arvind
A
Boykin
David W
DW
Wilson
W David
WD
D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology; D001483:Base Sequence; D001550:Benzamidines / Q000737:chemistry* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects; D010419:Pentamidine / Q000737:chemistry / Q000494:pharmacology; D011067:Poly dA-dT / Q000737:chemistry*; D013816:Thermodynamics; D014466:Ultraviolet Rays
D000977:Antiparasitic Agents; D001550:Benzamidines; D011067:Poly dA-dT; D010419:Pentamidine; C033286:furamidine; D004247:DNA