Synthesis and hybridization studies of oligonucleotides containing 1-(2-deoxy-2-alpha-C-hydroxymethyl-beta-D-ribofuranosyl)thymine (2'-alpha-hm-dT).
We report the first investigation of oligoribonucleotides containing a few 1-(2-deoxy-2-alpha-C-hydroxymethyl-beta-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; DeltaT(m) approximately -3 degrees C/insert), we find that 2',5'-linked H have a smaller effect on 2',5'-RNA:RNA and RNA:RNA duplexes (DeltaT(m) = -0.3 degrees C and -1.2 degrees 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 degrees C and -3.6 degrees 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 (DeltaT(m) = +1.5 degrees C/insert). These results are rationalized in terms of the compact and extended conformations of nucleotides.
Peng
Chang Geng
CG
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC, Canada H3A 2K6.
Damha
Masad J
MJ
D002942:Circular Dichroism; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D020871:RNA Stability; D013696:Temperature; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry
C092357:3'-deoxypsicothymidine; D009843:Oligoribonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D012313:RNA; D013936:Thymidine