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The interactions of phenanthroline compounds with DNAs: preferential binding to telomeric quadruplex over duplex.

Research paper by Lihua L Wang, Yanbo Y Wu, Tinggui T Chen, Chunying C Wei

Indexed on: 04 Sep '12Published on: 04 Sep '12Published in: International Journal of Biological Macromolecules



Abstract

Compounds that bind and stabilize selectively human telomeric quadruplex DNA structures are of significant interest due to their potential to inhibit telomerase and to halt tumor cell proliferation. In our previous study, we found that three novel phenanthroline derivatives could induce and stabilize significantly the formation of an antiparallel structure of human telomeric G-quadruplex DNA (G(3)(T(2)AG(3))(3)), moreover, these compounds could bind selectively to G-quadruplex over duplex. In order to understand their binding nature, in this work we investigated the interactions of compounds 1-3 with human telomeric G-quadruplex and i-motif (C(3)(A(2)TC(3))(3)) DNAs together with calf thymus DNAs (ct DNA) by means of absorption, fluorescence and CD spectroscopies and competition dialysis assay. Results showed that all three compounds showed the highest affinity for G-quadruplex structure although with least affinity for ct DNA. Compounds 1-3 could also stabilize the structure of i-motif with an increase in melting temperature (ΔT(m)) of 7.6, 7.2 and 10.1°C, respectively, in the presence of 10 times excess of compounds. Their binding stoichiometric ratios were 2:1 and 1:1 for G-quadruplex and i-motif DNAs, respectively. The thermodynamic parameters results indicated that the binding of compound to either quadruplex or duplex DNAs was entropically driven and hydrophobic force played a major role in the reaction.