[EN] SYNTHESIS OF BACKBONE MODIFIED MORPHOLINO OLIGONUCLEOTIDES AND CHIMERAS USING PHOSPHORAMIDITE CHEMISTRY<br/>[FR] SYNTHÈSE D'OLIGONUCLÉOTIDES MORPHOLINO MODIFIÉS PAR SQUELETTE ET CHIMÈRES UTILISANT LA CHIMIE PHOSPHORAMIDITE
申请人:UNIV COLORADO REGENTS
公开号:WO2018057430A1
公开(公告)日:2018-03-29
Amine substituted morpholino oligonucleotides, other than the classical N,N-dimethylamino PMO analogue, and methods of efficiently synthesizing these oligonucleotides with high yield are provided. Morpholino oligonucleotides having thiophosphoramidate, phosphoramidate, phosphoramidate diester, and alkyl phosphoramidate linkers. Chimeras containing unmodified DNA/RNA and other analogs of DNA/RNA can be prepared. These oligonucleotides form duplexes with complementary DNA or RNA that are more stable than natural DNA or DNA/RNA complexes, are active with RNAse H1, and may be transfected into cells using standard lipid reagents. These analogues are therefore useful for numerous applications.
提供了替代传统N,N-二甲基氨基PMO类似物的吗啉基寡核苷酸以及高产率有效合成这些寡核苷酸的方法。这些寡核苷酸具有硫代磷酰胺酸酰胺、磷酸酰胺酰胺、磷酸酰胺二酯和烷基磷酰胺酰胺连接基。可以制备含有未修饰DNA/RNA和其他DNA/RNA类似物的嵌合体。这些寡核苷酸与互补的DNA或RNA形成的双链比天然DNA或DNA/RNA复合物更稳定,与RNA酶H1活性,可以使用标准脂质试剂转染到细胞中。因此,这些类似物在许多应用中非常有用。