INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
Conformational states of 2'-C-methylpyrimidine nucleosides in single and double nucleic acid stranded structures
LAURA ROBALDO; RODRIGO PONTIGGIA; SANTIAGO DI LELLA; DARÍO ESTRÍN; JOACHIN ENGELS; ADOLFO IRIBARREN; JAVIER MONTSERRAT
JOURNAL OF PHYSICAL CHEMISTRY B - (Print)
AMER CHEMICAL SOC
Lugar: Washington; Año: 2013 vol. 117 p. 57 - 57
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 deltaTm decrease (-8.9 to -12.5ºC), while circular dichroism experiments indicated that the helix was still A-type, suggesting a localized disturbance disorder. Therefore, 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 explain the behavior of the 2´-deoxy-2´-C-methyl nucleosides in single stranded environments, like 10-23 DNAzyme core, molecular dynamic simulations were performed, incorporating the modified analogs into single stranded reported stem-loop structures, studding the sugar conformations along the MD trajectories. It was observed that although their preferential conformational states, the 2´-C-methyl analogs are flexible enough to adopt a different puckering in single stranded environments.