Thermodynamic contributions of the reactions of DNA intramolecular structures with their complementary strands

Hui Ting Lee, Chris M. Olsen, Lela Waters, Holly Sukup, Luis A Marky

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Abstract

One focus of our research is to further our understanding of the physico-chemical properties of unusual DNA structures and their interaction with complementary oligonucleotides. We have investigated three types of reactions involving the interaction of intramolecular DNA complexes with their complementary single strands of varied length. Specifically, we have used a combination of isothermal titration (ITC) and differential scanning (DSC) calorimetry and spectroscopy techniques to determine standard thermodynamic profiles for the reaction of an i-motif, G-quadruplex, and triplex with their complementary strands. The enthalpies for each reaction are measured directly in ITC titrations and compared with those obtained indirectly from Hess cycles using DSC unfolding data. All reactions investigated yielded favorable free energy contributions, indicating that each single strand is able to invade and disrupt the corresponding intramolecular DNA complex. These favorable free energy terms are enthalpy driven, which result from a compensation of exothermic contributions, due to the formation of additional base-pair stacks (or base-triplet stacks) in the duplex product (or triplex product), immobilization of electrostricted water by the base-pair and base-triplet stacks, and the removal of structural water from the reactant single strands; and endothermic contributions from the disruption of base-base stacking interactions of the reactant single strands. This investigation of nucleic acid reactions has provided new methodology, based on physico-chemical principles, to determine the molecular forces involved in the interactions between DNA nucleic acid structures. This methodology may be used in targeting reactions for the control of gene expression.

Original languageEnglish (US)
Pages (from-to)1052-1063
Number of pages12
JournalBiochimie
Volume90
Issue number7
DOIs
Publication statusPublished - Jul 1 2008

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Keywords

  • Antisense
  • DSC
  • ITC
  • Intramolecular DNA structures
  • Targeting nucleic acids
  • Thermodynamics

ASJC Scopus subject areas

  • Biochemistry

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