title: Synthesis and hybridization studies of oligonucleotides containing 1-(2-deoxy-2-alpha-C-hydroxymethyl-beta-D-ribofuranosyl)thymine (2'-alpha-hm-dT).
abstract: 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.
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC, Canada H3A 2K6.
authors.forename: Chang Geng
authors.initials: CG
authors.lastname: Peng
authors.forename: Masad J
authors.initials: MJ
authors.lastname: Damha
mesh_terms: 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
chemical_list: C092357:3'-deoxypsicothymidine; D009843:Oligoribonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D012313:RNA; D013936:Thymidine