Synthesis and thermodynamics of oligonucleotides containing chirally pure R(P) methylphosphonate linkages.
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.
Reynolds
M A
MA
Genta Inc., San Diego, CA 92121, USA.
Hogrefe
R I
RI
Jaeger
J A
JA
Schwartz
D A
DA
Riley
T A
TA
Marvin
W B
WB
Daily
W J
WJ
Vaghefi
M M
MM
Beck
T A
TA
Knowles
S K
SK
Klem
R E
RE
Arnold
L J
LJ
D002851:Chromatography, High Pressure Liquid; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry*
D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C032627:methylphosphonic acid