Published online 28 June 2004
Nucleic Acids Research, Vol. 32 No. 11 © Oxford University Press 2004; all rights reserved
Thermodynamic and structural characterization of 2'-nitrogen-modified RNA duplexes
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208-3500, USA
* To whom correspondence should be addressed. Tel: +1 847 467 6880; Fax: +1 847 491 2467; Email: erik{at}northwestern.edu
Received May 11, 2004; Revised and Accepted June 1, 2004
2'-aminonucleosides are commonly used as sites of post-synthetic chemical modification within nucleic acids. As part of a larger cross-linking strategy, we appended alkyl groups onto the N2' position of 2'-amino-modified RNAs via 2'-ureido and 2'-amido linkages. We have characterized the thermodynamics of 2'-amino, 2'-alkylamido and 2'-alkylureido-modified RNA duplexes and show that 2'-ureido-modified RNAs are significantly more stable than analogous 2'-amido-modified RNAs. Using NMR spectroscopy and NMR-based molecular modeling of 2'-modified RNA duplexes, we examined the effects that 2'-nitrogen modifications have on RNA helices. Our data suggest that the 2'-ureido group forms a specific intra-nucleoside interaction that cannot occur within 2'-amido-modified helices. These results indicate that 2'-ureido modifications are superior to analogous 2'-amido ones for applications that require stable base pairing.