title: Design, synthesis, and duplex-stabilizing properties of conformationally constrained tricyclic analogues of LNA.
abstract: The design, synthesis and biophysical evaluation of two highly-constrained tricyclic analogues of locked nucleic acid (LNA), which restrict rotation around the C4'-C5'-exocyclic bond (torsion angle γ) and enhance hydrophobicity in the minor groove and along the major groove, are reported. A structural model that provides insights into the sugar-phosphate backbone conformations required for efficient hybridization to complementary nucleic acids is also presented.
authors.affiliation: Department of Chemistry, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QC H3C 3J7, Canada. stephen.hanessian@umontreal.ca.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Giacometti
authors.affiliation: Department of Chemistry, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QC H3C 3J7, Canada. stephen.hanessian@umontreal.ca.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Salinas
authors.affiliation: Department of Medicinal Chemistry, Ionis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, USA. PSeth@ionisph.com.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Østergaard
authors.affiliation: Department of Medicinal Chemistry, Ionis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, USA. PSeth@ionisph.com.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Swayze
authors.affiliation: Department of Medicinal Chemistry, Ionis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, USA. PSeth@ionisph.com.
authors.forename: Punit P
authors.initials: PP
authors.lastname: Seth
authors.affiliation: Department of Chemistry, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QC H3C 3J7, Canada. stephen.hanessian@umontreal.ca.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
mesh_terms: D015195:Drug Design; D008968:Molecular Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; C477371:locked nucleic acid