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Identification of a Tricyclic P III Chiral Auxiliary for Solid‐Supported Synthesis of Stereopure Phosphorothioate‐Containing Oligonucleotides
Author(s) -
Sakamuri Sukumar,
Liu Dingguo,
Eltepu Laxman,
Liu Bin,
Reboton Lisa Jo,
Preston Ryan,
Bradshaw Curt W.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900631
Subject(s) - oligonucleotide , nuclease , combinatorial chemistry , chemistry , tricyclic , nucleic acid , dna , rna , stereochemistry , biochemistry , gene
Since the recognition of oligonucleotides as a therapeutic modality, significant work has been devoted to improving therapeutic properties, including nuclease stability. Phosphorothioate (PS) modifications of phosphodiesters are one of the most explored chemical modification and integral to currently approved oligonucleotide therapeutics, including antisense oligonucleotides (ASOs) and short interfering RNAs (siRNAs). Insertion of sulfur into the phosphate bridge in an n ‐mer leads to 2 n isomeric mixtures of PSs, with different nuclease stability and protein‐binding properties. Efforts to create stereopure PS‐containing oligonucleotides has spurred interest in identifying new synthetic methods. Herein, work on a novel and practical tricyclic P III chiral auxiliary and its application in solid‐supported synthesis of stereopure PS‐containing oligonucleotides is reported.