title: Effects of locked nucleic acid substitutions on the stability of oligonucleotide hairpins.
abstract: An understanding of the stability of nucleic acid folding is critical for applications involving RNA viruses, small molecule-RNA binding, and therapeutics, for example. To explore factors that affect this stability, hairpins made from oligonucleotides containing both a GAAA tetraloop and three to five complements in the stem have been used as models where locked nucleic acids (LNAs) have been substituted into the sequence. UV spectroscopy was used to obtain melting curves in 20% by volume formamide, and the enthalpies and entropies of melting were determined. Although LNA substitutions typically increase the stability of a hybrid, we have found a decrease in stability for DNA and RNA GAAA hairpins when LNA is substituted into the loop. Tetraloops synthesized from natural bases show higher enthalpies and entropies of melting compared to the LNA substituted sequences indicating that LNA substitutions can destabilize a hairpin but stabilize the corresponding double stranded structure.
authors.affiliation: Chemistry Department, State University of New York at New Paltz, New Paltz, New York 12561, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Hull
authors.forename: Corinne
authors.initials: C
authors.lastname: Szewcyk
authors.forename: Pamela M
authors.initials: PM
authors.lastname: St John
mesh_terms: D004247:DNA / Q000737:chemistry*; D005559:Formamides / Q000737:chemistry; D055029:Inverted Repeat Sequences; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D020871:RNA Stability; D013057:Spectrum Analysis; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D005559:Formamides; D009841:Oligonucleotides; C477371:locked nucleic acid; C031066:formamide; D012313:RNA; D004247:DNA