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Biochimie

Interaction of minor groove ligands with G-quadruplexes: thermodynamic contributions of the number of quartets, T-U substitutions, and conformation.


PMID 21684318

Abstract

In the presence of specific metal ions, DNA oligonucleotides containing guanine repeat sequences can adopt G-quadruplex structures. In this work, we used a combination of spectroscopic and calorimetric techniques to investigate the conformation and unfolding thermodynamics of the K(+)-form of five G-quadruplexes with sequences: d(G(2)T(2)G(2)TGTG(2)T(2)G(2)), G2, d(G(3)T(2)G(3)TGTG(3)T(2)G(3)), G3, their analogs where T is replaced with U, G2-U and G3-U, and r(G(2)U(2)G(2)UGUG(2)U(2)G(2)), rG2. These G-quadruplexes show CD spectra characteristic of the "chair" conformation (G2 and G2-U), or "basket" conformation (rG2); or a mixture of these two conformers (G3 and G3-U). Thermodynamic profiles show that the favorable folding of each G-quadruplex results from the typical compensation of a favorable enthalpy and unfavorable entropy contributions. G-quadruplex stability increase in the following order (in ΔG°(20)): rG2 (-1.3 kcal/mol) < G2 < G2-U

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