title: Thermal stability and conformation of antiparallel duplexes formed by P-stereodefined phosphorothioate DNA/LNA chimeric oligomers with DNA and RNA matrices.
abstract: 3'-O-(2-Thio-4,4-pentamethylene-1,3,2-oxathiaphospholane) derivatives of LNA-type nucleosides (LNA-OTPs, 2a-d; B' = Thy, Ade(Bz), Cyt(Bz), Gua(dmf), respectively) were synthesized and separated into pure P-diastereomers. X-ray analysis allowed for assignment of the absolute configuration of the phosphorus atom in the detritylated, fast-eluting diastereomer 2a. The diastereomerically pure LNA-OTP monomers were used in solid phase synthesis of P-stereodefined chimeric PS-(DNA/LNA) 11-mers containing 2-3 LNA units. Formally, among the phosphorothioate oligomers the biggest enhancement in thermal stability of Watson-Crick paired duplexes was found for [SP-PS]-(DNA/LNA)/RNA duplexes (on average 8.2 °C per LNA nucleotide), followed by [RP-PS]-(DNA/LNA)/RNA (6.3 °C), [RP-PS]-(DNA/LNA)/DNA (3.8 °C) and [SP-PS]-(DNA/LNA)/DNA (2.4 °C per LNA nucleotide). However, detailed analysis of the thermal dissociation data showed that the thermal stability of (PS-LNA)-containing duplexes does not depend on the spatial orientation of the sulfur atoms. This conclusion received support from CD measurements.
authors: Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Łódź, Poland. pguga@cbmm.lodz.pl.
authors: Katarzyna
authors: K
authors: Jastrzębska
authors: Anna
authors: A
authors: Maciaszek
authors: Rafał
authors: R
authors: Dolot
authors: Grzegorz
authors: G
authors: Bujacz
authors: Piotr
authors: P
authors: Guga
mesh_terms: D001483:Base Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000737:chemistry*; D054735:Phosphorothioate Oligonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D009841:Oligonucleotides; D054735:Phosphorothioate Oligonucleotides; C477371:locked nucleic acid; D012313:RNA; D004247:DNA