Energetic aspects of locked nucleic acids quadruplex association and dissociation |
| |
Authors: | Petraccone Luigi Erra Eva Randazzo Antonio Giancola Concetta |
| |
Affiliation: | Dipartimento di Scienze Farmaceutiche, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy. |
| |
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. |
| |
Keywords: | locked nucleic acids quadruplex circular dichroism kinetics |
本文献已被 PubMed 等数据库收录! |
|