Reynolds M A, Hogrefe R I, Jaeger J A, Schwartz D A, Riley T A, Marvin W B, Daily W J, Vaghefi M M, Beck T A, Knowles S K, Klem R E, Arnold L J
Genta Inc., San Diego, CA 92121, USA.
Nucleic Acids Res. 1996 Nov 15;24(22):4584-91. doi: 10.1093/nar/24.22.4584.
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.
甲基膦酸酯（MP）寡脱氧核苷酸（MPO）是传统DNA的代谢稳定类似物，其中一个非键合磷酰氧被甲基取代。合成了所有16种可能的手性R(P) MP二核苷酸，并进行衍生化以用于自动化寡核苷酸合成。这些二聚体合成子可用于制备（i）在每隔一个位置具有确定R(P) 手性的全MP连接寡核苷酸（R(P) 手性富集MPO）或（ii）交替的R(P) MP/磷酸二酯主链寡核苷酸，具体取决于3'-偶联基团的组成。还制备了具有2'-O-甲基糖修饰的手性纯二聚体合成子。用这些R(P) 手性甲基膦酸酯连接合成子制备的寡核苷酸与RNA的结合亲和力明显高于外消旋MPO。
