title: Solid-phase chemical synthesis of phosphonoacetate and thiophosphonoacetate oligodeoxynucleotides.
abstract: Phosphonoacetate and thiophosphonoacetate oligodeoxynucleotides were prepared via a solid-phase synthesis strategy. Under Reformatsky reaction conditions, novel esterified acetic acid phosphinodiamidites were synthesized and condensed with appropriately protected 5'-O-(4, 4'-dimethoxytrityl)-2'-deoxynucleosides to yield 3'-O-phosphinoamidite reactive monomers. These synthons when activated with tetrazole were used with an automated DNA synthesizer to prepare phosphonoacetic acid modified internucleotide linkages on controlled pore glass. The phosphinoacetate coupling products were quantitatively oxidized at each step with (1S)-(+)-(10-camphorsulfonyl)oxaziridine or 3H-1,2-benzodithiol-3-one-1,1-dioxide to produce mixed sequence phosphonoacetate and thiophosphonoacetate oligodeoxynucleotides with an average per cycle coupling efficiency of greater than 97%. Completely deprotected, modified oligodeoxynucleotides were purified by reverse-phase HPLC and characterized by ion exchange HPLC, (31)P NMR, and MALDI/TOF mass spectroscopy. Both analogues were stable toward hydrolysis with snake venom phosphodiesterase and stimulated RNase H1 activity.
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Dellinger
authors.forename: David M
authors.initials: DM
authors.lastname: Sheehan
authors.forename: Nanna K
authors.initials: NK
authors.lastname: Christensen
authors.forename: James G
authors.initials: JG
authors.lastname: Lindberg
authors.forename: Marvin H
authors.initials: MH
authors.lastname: Caruthers
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D019906:Nuclear Magnetic Resonance, Biomolecular; D009841:Oligonucleotides / Q000138:chemical synthesis*; D063086:Organothiophosphates / Q000138:chemical synthesis*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009841:Oligonucleotides; D063086:Organothiophosphates; D010746:Phosphonoacetic Acid