Abstract
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. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 584–594, 2006
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]