title: Comparison of duplex stabilizing properties of 2'-fluorinated nucleic acid analogues with furanose and non-furanose sugar rings.
abstract: We compare the duplex stabilizing properties of 2'-fluorinated nucleic acid analogues with furanose and non-furanose ring systems and dissect the relative contributions of hydration, sugar conformation, and fluorine configuration toward the overall T(m) value. We find that the stabilization imparted by fluorine substitution is additive over that obtained by restricting the conformation of the sugar ring itself. Our studies support further evaluation of fluorinated nucleic acid analogues with non-furanose sugar rings as surrogates of 2'-F RNA for therapeutic antisense applications.
authors.affiliation: Department of Medicinal Chemistry, Isis Pharmaceuticals, Inc. , 2855 Gazelle Court, Carlsbad, California 92010, United States.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Østergaard
authors.forename: Timothy
authors.initials: T
authors.lastname: Dwight
authors.forename: Andres
authors.initials: A
authors.lastname: Berdeja
authors.forename: Eric E
authors.initials: EE
authors.lastname: Swayze
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jung
authors.forename: Punit P
authors.initials: PP
authors.lastname: Seth
mesh_terms: D020029:Base Pairing; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D012266:Ribose / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D009696:Nucleic Acids; D012313:RNA; D012266:Ribose