Novel 2'/3'/5'-(R/S)-Serinyl Functionalized Oligonucleotides

摘要

The present invention provides novel chiral serinyl functionalized tethered oligunucleotides i.e. R/S serinyl functionalized tethered oligonucleotides and the process of preparation thereof. Specifically, the present invention provides a modified nucleoside unit containing the R/S serinyl derivative at 2′ of the sugar unit which is introduced in a nucleotide sequence. Also, capping of the oligonucleotides with abasic serinyl derivative to render the nuclease stability to the oligonucleotiedds is also disclosed. The chiral serinyl functionalized tethered oligonucleotides, 2′-O-[R/S-(2-amino-3-methoxy)propyl] nucleic acids with both ′3- and 5′-ends capped with two units of abasic serine have antisense activity against the miRNA.

主权项

1. A novel chiral serinyl functionalized tethered oligonucleotide having Formula I, wherein, X is selected from the group consisting of ‘O’ or ‘S’; Y is selected from the group consisting of OH, SH, OR, SR or OP, NH2, NHR, NR2 where R is (C1-C10) alkyl, heteroaryl, aryl, alkyl aryl and P is a protecting group selected from the group consisting of Cbz, TFA, DMT,TBS,TMS; Z is selected from the group consisting of NH2, NHR, NHR2, guanidine or NHP or OR, SR; where R is H, (C1-C10) alkyl, heteroaryl, aryl, alkyl aryl and P is a protecting group selected from the group consisting of Cbz, TFA, DMT,TBS,TMS, where “ONs” is oligonucleotide(s),Provided that Y is OH, OR or OP and Z is other than OR or SR.