Chemical synthesis of LNA-2-thiouridine and its influence on stability and selectivity of oligonucleotide binding to RNA.

作者: Marta Carlucci , Elzbieta Kierzek , Anna Olejnik , Douglas H. Turner , Ryszard Kierzek

DOI: 10.1021/BI901506F

关键词: OligonucleotideThiouridineRNA interferenceRNARiboseNuclease protection assayCombinatorial chemistryChemistrySelectivityBiochemistryBase pair

摘要: Hybridization to RNA is important for many applications, including antisense therapeutics, interference, and microarray screening. Similar thermodynamic stabilities of A-U G-U base pairs result in difficulties selective binding RNA. Moreover, are weaker than G-C so that sometimes weak when present. It known, however, replacement uridine with 2-thiouridine significantly improves selectivity. To test additional improvement the specificity A over G, LNA-2-thiouridine was synthesized first time incorporated into LNA-2'-O-methyl-RNA/RNA duplexes. UV melting used measure effect replacing 2'-O-methyluridine 2'-O-methyl-2-thiouridine or LNA-2-thiouridine. The usually enhances Selectivity optimized a single placed at an internal position duplex.

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