title: Conformational states of 2'-C-methylpyrimidine nucleosides in single and double nucleic acid stranded structures.
abstract: The hybridization performance of a set of 12-mer RNA:RNA duplexes containing 2'-C-methyluridine, 5-bromo-2'-C-methyluridine, or (2'S)-2'-deoxy-2'-C-methyluridine was analyzed. Melting point temperatures of the modified duplexes showed an important ΔT(m) decrease (-8.9 to -12.5 °C), while circular dichroism experiments indicated that the helix was still A-type, suggesting a localized disturbance disorder. Molecular dynamics simulations using AMBER were carried out in order to gain structural knowledge about the effect of the 2'-C-methyl modification in double stranded environments. On the other hand, in an attempt to explain the behavior of the 2'-deoxy-2'-C-methyl nucleosides in single stranded environments, like the 10-23 DNAzyme core, molecular dynamic simulations were performed, incorporating the modified analogues into single stranded reported stem-loop structures, studding the sugar conformations along the MD trajectories. It was observed that, despite their preferential conformational states, the 2'-C-methyl analogues are flexible enough to adopt a different puckering in single stranded environments.
authors.affiliation: INGEBI (CONICET), Vuelta de Obligado 2490, Buenos Aires (1428), Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Robaldo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pontiggia
authors.forename: Santiago
authors.initials: S
authors.lastname: Di Lella
authors.forename: Darío A
authors.initials: DA
authors.lastname: Estrin
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Engels
authors.forename: Adolfo M
authors.initials: AM
authors.lastname: Iribarren
authors.forename: Javier M
authors.initials: JM
authors.lastname: Montserrat
mesh_terms: D002942:Circular Dichroism; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D011741:Pyrimidine Nucleosides / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D009696:Nucleic Acids; D011741:Pyrimidine Nucleosides