title: Solid phase synthesis of oligodeoxyribonucleoside phosphorodithioates from thiophosphoramidites.
abstract: Oligonucleoside phosphorodithioates 1 are modified DNA sequences with potential use as antisense oligonucleotides. The preparation of up to 20-mers containing all four bases by solid phase synthesis is described, with details on the preparation of the four monomer units (protected nucleoside thiophosphoramidites 2), the conditions used for the assembly of the strands with up to 19 phosphorodithioate linkages, and the purification and characterisation of the products. Full-length homogeneity of HPLC-purified all-phosphorodithioate products is demonstrated by PAGE, but 31P NMR discloses the presence of phosphorothioate impurities (typically 8-9%), the origin of which is discussed. Oligonucleoside phosphorodithioates are freely soluble in water at neutral or basic pH, and are very stable towards oxidation, hydrolysis, and nuclease cleavage. Their ability to hybridize to complementary DNA has been studied by UV melting point (Tm) measurements. The observed depression of Tm, 0.5-2 degrees C per phosphorodithioate linkage, is higher that the 0.4-0.6 degrees C found for phosphorothioates.
authors.affiliation: Department of Chemistry, HC Orsted Institute, University of Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Bjergårde
authors.forename: O
authors.initials: O
authors.lastname: Dahl
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification; D009946:Organothiophosphorus Compounds / Q000737:chemistry*; D013696:Temperature; D013873:Thionucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification
chemical_list: D009838:Oligodeoxyribonucleotides; D009946:Organothiophosphorus Compounds; D013873:Thionucleotides