Published online 23 December 2005
Article |
Synthesis and hybridization studies of oligonucleotides containing 1-(2-deoxy-2-
-C-hydroxymethyl-ß-D-ribofuranosyl)thymine (2'--hm-dT)
Department of Chemistry, McGill University 801 Sherbrooke Street West, Montreal, QC, Canada H3A 2K6
*To whom correspondence should be addressed. Tel: +1 514 398 7552; Fax: +1 514 398 3797; Email: masad.damha{at}mcgill.ca
Received September 8, 2005. Revised November 17, 2005. Accepted November 17, 2005.
We report the first investigation of oligoribonucleotides containing a few 1-(2-deoxy-2-
-C-hydroxymethyl-ß-D-ribofuranosyl)thymine units (or 2'-hm-dT, abbreviated in this work as ‘H’). Both the 2'-CH2O-phosphoramidite and 3'-O-phosphoramidite derivatives of H were synthesized and incorporated into both 2',5'-RNA and RNA chains. The hybridization properties of the modified oligonucleotides have been studied via thermal denaturation and circular dichroism studies. While 3',5'-linked H was shown previously to significantly destabilize DNA:RNA hybrids and DNA:DNA duplexes (modification in the DNA strand; 
Tm 
–3°C/insert), we find that 2',5'-linked H have a smaller effect on 2',5'-RNA:RNA and RNA:RNA duplexes (Tm = –0.3°C and –1.2°C, respectively). The incorporation of 3',5'-linked H into 2',5'-RNA:RNA and RNA:RNA duplexes was found to be more destabilizing (–0.7°C and –3.6°C, respectively). Significantly, however, the 2',5'-linked H units confer marked stability to RNA hairpins when they are incorporated into a 2',5'-linked tetraloop structure (Tm = +1.5°C/insert). These results are rationalized in terms of the compact and extended conformations of nucleotides.