title: A thermodynamic approach for the targeting of nucleic acid structures using their complementary single strands.
abstract: The main focus of our investigations is to further our understanding of the physicochemical properties of nucleic acid structures. We report on a thermodynamic approach to study the reaction of a variety of intramolecular nucleic acid structures with their respective complementary strands. Specifically, we have used a combination of isothermal titration (ITC) and differential scanning calorimetry (DSC) and spectroscopy techniques to determine standard thermodynamic profiles for the reaction of a triplex, G-quadruplex, hairpin loops, pseudoknot, and three-arm junctions with their complementary strands. Reaction enthalpies 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 structure. These favorable free energy terms are enthalpy-driven, resulting from a favorable compensation of exothermic contributions due to the formation of additional base-pair stacks in the duplex product, and endothermic contributions, from the disruption of base stacking contributions of the reactant single strands. The overall results provide a thermodynamic approach that can be used in the targeting of nucleic acids, especially the secondary structures formed by mRNA, with oligonucleotides for the control of gene expression.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Lee
authors.forename: Caroline
authors.initials: C
authors.lastname: Carr
authors.forename: Hollie
authors.initials: H
authors.lastname: Siebler
authors.forename: Lela
authors.initials: L
authors.lastname: Waters
authors.forename: Irine
authors.initials: I
authors.lastname: Khutsishvili
authors.forename: Fany
authors.initials: F
authors.lastname: Iseka
authors.forename: Brian
authors.initials: B
authors.lastname: Domack
authors.forename: Chris M
authors.initials: CM
authors.lastname: Olsen
authors.forename: Luis A
authors.initials: LA
authors.lastname: Marky
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D018076:DNA, Complementary / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry; D054856:G-Quadruplexes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D018076:DNA, Complementary; D004277:DNA, Single-Stranded; D009841:Oligonucleotides; C051802:triplex DNA; D012313:RNA; D004247:DNA