title: Synthesis and thermodynamics of oligonucleotides containing chirally pure R(P) methylphosphonate linkages.
abstract: Methylphosphonate (MP) oligodeoxynucleotides (MPOs) are metabolically stable analogs of conventional DNA containing a methyl group in place of one of the non-bonding phosphoryl oxygens. All 16 possible chiral R(P) MP dinucleotides were synthesized and derivatized for automated oligonucleotide synthesis. These dimer synthons can be used to prepare (i) all-MP linked oligonucleotides having defined R(P) chirality at every other position (R(P) chirally enriched MPOs) or (ii) alternating R(P) MP/phosphodiester backbone oligonucleotides, depending on the composition of the 3'-coupling group. Chirally pure dimer synthons were also prepared with 2'-O-methyl sugar modifications. Oligonucleotides prepared with these R(P) chiral methylphosphonate linkage synthons bind RNA with significantly higher affinity than racemic MPOs.
authors.affiliation: Genta Inc., San Diego, CA 92121, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Reynolds
authors.forename: R I
authors.initials: RI
authors.lastname: Hogrefe
authors.forename: J A
authors.initials: JA
authors.lastname: Jaeger
authors.forename: D A
authors.initials: DA
authors.lastname: Schwartz
authors.forename: T A
authors.initials: TA
authors.lastname: Riley
authors.forename: W B
authors.initials: WB
authors.lastname: Marvin
authors.forename: W J
authors.initials: WJ
authors.lastname: Daily
authors.forename: M M
authors.initials: MM
authors.lastname: Vaghefi
authors.forename: T A
authors.initials: TA
authors.lastname: Beck
authors.forename: S K
authors.initials: SK
authors.lastname: Knowles
authors.forename: R E
authors.initials: RE
authors.lastname: Klem
authors.forename: L J
authors.initials: LJ
authors.lastname: Arnold
mesh_terms: D002851:Chromatography, High Pressure Liquid; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C032627:methylphosphonic acid