title: Analogues of a locked nucleic acid with three-carbon 2',4'-linkages: synthesis by ring-closing metathesis and influence on nucleic acid duplex stability and structure.
abstract: Two bicyclic 2'-deoxynucleoside analogues containing a saturated and an unsaturated three-carbon 2',4'-linkage, respectively, have been synthesized using a ring-closing metathesis-based linear strategy starting from uridine. Both analogues have been incorporated into oligodeoxynucleotide sequences and increased the stability of DNA:RNA hybrid duplexes (DeltaT(m) approximately 2.5-5.0 degrees C per modification) and decreased the stability of dsDNA duplexes (DeltaT(m) approximately 2.5-1.0 degrees C per modification). CD spectroscopy revealed that the bicyclic nucleosides induced formation of A-type-like duplexes albeit to a lesser degree than found for locked nucleic acid (LNA) monomers. From the CD data and UV melting analysis, we propose that the 2'-oxygen atom of the bicyclic moiety is essential for the formation of stabilized A-type-like dsDNA but not for the formation of a stabilized A-type DNA:RNA hybrid.
authors.affiliation: Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Nanna
authors.initials: N
authors.lastname: Albaek
authors.forename: Michael
authors.initials: M
authors.lastname: Petersen
authors.forename: Poul
authors.initials: P
authors.lastname: Nielsen
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013696:Temperature; D014529:Uridine
chemical_list: D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid; D012313:RNA; D004247:DNA; D014529:Uridine