Energetic aspects of locked nucleic acids quadruplex association and dissociation.
The design of modified nucleic acid aptamers is improved by considering thermodynamics and kinetics of their association/dissociation processes. Locked Nucleic Acids (LNA) is a promising class of nucleic acid analogs. In this work the thermodynamic and kinetic properties of a LNA quadruplex formed by the TGGGT sequence, containing only conformationally restricted LNA residues, are reported and compared to those of 2'-OMe-RNA (O-RNA) and DNA quadruplexes. The thermodynamic analysis indicates that the sugar-modified quadruplexes (LNA and O-RNA) are stabilized by entropic effects. The kinetic analysis shows that LNA and O-RNA quadruplexes are characterized by a slower dissociation and a faster association with respect to DNA quadruplex. Interestingly, the LNA quadruplex formation process shows a second-order kinetics with respect to single strand concentration and has a negative activation energy. To explain these data, a mechanism for tetramer formation with two intermediate states was proposed.
Petraccone
Luigi
L
Dipartimento di Scienze Farmaceutiche, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy.
Erra
Eva
E
Randazzo
Antonio
A
Giancola
Concetta
C
D020029:Base Pairing / Q000502:physiology*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D054856:G-Quadruplexes; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid; D004247:DNA