Synthesis of backbone modified morpholino oligonucleotides and chimeras using phosphoramidite chemistry

摘要

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.