Synthesis and hybridization studies of oligonucleotides containing 1-(2-deoxy-2--C-hydroxymethyl-?-D-ribofuranosyl)thymine (2'--hm-dT) - Oligonucleotides

Synthesis and hybridization studies of oligonucleotides containing 1-(2-deoxy-2--C-hydroxymethyl-?-D-ribofuranosyl)thymine (2'--hm-dT)
Published online 23 December 2005
Chang Geng Peng and Masad J. Damha
Nucleic Acids Research 2005
We report the first investigation of oligoribonucleotides containing a few 1-(2-deoxy-2--C-hydroxymethyl-?-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.
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