Cooperative Binding of 8-mer Oligonucleotides Containing 5-(1-Propynyl)-2'-deoxyuridine to Adjacent DNA Sites by Triple-Helix Formation

Abstract

The design of cooperative domains between DNA-binding ligands for modulation of the kinetics and thermodynamics of ligand- nucleic acid interactions is at an early stage of development. Pyrimidine oligodeoxyribonucleotides 11 nucleotides (nt) in length are known to bind cooperatively to abutting sites on double-helical DNA by triple-helix formation, resulting in a 20-fold increase in the association constant for one oligonucleotide in the presence of the neighboring oligonucleotide. This 1.8 kcal·mol^(-1) interaction energy may arise from π-stacking between the bases at the triple-helical junction. The incorporation of discrete dimerization domains to oligonucleotides such as those capable of forming a short Watson-Crick helix produces a cooperative interaction and results in a 44-fold enhancement in the association constant of one oligonucleotide in the presence of a neighbor.

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