Communication à un colloque
Résumé : LNA, conformationally restricted nucleotide analogs, constitute an important addition to the tools available for nucleic acid diagnostics and nucleic acid therapeutics. LNA monomers contain a modified ribose moiety which locks the sugar, via a 2’O - 4’C methylene bridge, into the C3’-endo/N-type conformation. LNA resemble natural nucleic acids with respect to Watson-Crick base pairing and the potential of LNA containing oligonucleotides lies in their ability to mediate high affinity pairing with complementary RNA or DNA strands, with superior sequence specificity than their natural equivalent. With the aim to contribute to a better understanding of the origin of these effects at the molecular level, the hybridization thermodynamics of different oligonucleotides duplexes has been studied by Isothermal titration calorimetry (ITC). The systems studied differ by the nature and number of LNA nucleotides. The data obtained by ITC (ΔG°, ΔH°, S° and ΔCp) were correlated to structural information obtained by Circular Dichroïsm (CD) and Nuclear Magnetic Resonance (RMN) Spectroscopy. Even if much work is still needed to elucidate all the factors at the origin of the increase in thermodynamic and thermal stability of a duplex induced by LNA substitutions, it is clear that the combined use of different experimental tools (ITC, NMR, CD) helps to obtain a more complete picture at the molecular level.