Key result
Replacing uridine with LNA-2-thiouridine enhances RNA binding and selectivity, peaking with a single internal placement.
Why the study?
Similar thermodynamic stabilities of A-U and G-U base pairs cause difficulties in selective RNA binding, and A-U pairs often result in weak binding when abundant.
Synthesis and incorporation of LNA-2-thiouridine into oligonucleotide duplexes enhances binding stability and selectivity to RNA.
Hypothesis-generating for LNA-2-thiouridine in RNA-targeted oligos; further validation needed before therapeutic exploration.
Hybridization to RNA is important for many applications, including antisense therapeutics, RNA interference, and microarray screening. Similar thermodynamic stabilities of A-U and G-U base pairs result in difficulties in selective binding to RNA. Moreover, A-U pairs are weaker than G-C pairs so that binding is sometimes weak when many A-U pairs are present. It is known, however, that replacement of uridine with 2-thiouridine significantly improves binding and selectivity. To test for additional improvement of binding and of the specificity for binding A over G, LNA-2-thiouridine was synthesized for the first time and incorporated into many LNA-2'-O-methyl-RNA/RNA duplexes. UV melting was used to measure the thermodynamic effect of replacing 2'-O-methyluridine with 2'-O-methyl-2-thiouridine or LNA-2-thiouridine. The 2-thiouridine usually enhances binding and selectivity. Selectivity is optimized when a single 2-thiouridine is placed at an internal position in a duplex.
No takes yet. Share an insight, caveat, or question.
Carlucci et al. (2009) studied this question. LNA-2-thiouridine vs. 2'-O-methyluridine was evaluated on Thermodynamic stability and selectivity of binding to RNA. Replacement of uridine with LNA-2-thiouridine enhances binding and selectivity to RNA, with optimal selectivity achieved when a single 2-thiouridine is placed at an internal position in a duplex.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: