Abstract:
: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.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Carlucci M,Kierzek E,Olejnik A,Turner DH,Kierzek Rdoi
10.1021/bi901506fsubject
Has Abstractpub_date
2009-11-24 00:00:00pages
10882-93issue
46eissn
0006-2960issn
1520-4995journal_volume
48pub_type
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