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Chemical Synthesis of a Locked Nucleic Acid–Substituted Dinucleotide Cap Analog
Author(s) -
Shanmugasundaram Muthian,
Senthilvelan Annamalai,
Kore Anilkumar R.
Publication year - 2021
Publication title -
current protocols
Language(s) - English
Resource type - Journals
ISSN - 2691-1299
DOI - 10.1002/cpz1.22
Subject(s) - locked nucleic acid , guanosine , chemistry , regioselectivity , nucleic acid , combinatorial chemistry , catalysis , moiety , coupling reaction , tris , linker , stereochemistry , organic chemistry , biochemistry , dna , oligonucleotide , computer science , operating system
This article describes a reliable and efficient method for synthesis of the dinucleotide cap analog m 7(LNA) G[5′]ppp[5′]G containing a locked nucleic acid moiety. The required LNA intermediate for the final coupling reaction, m 7(LNA) GDP, is prepared in six steps starting from 5′‐DMTr‐ N ‐DMF LNA guanosine. The overall reaction involves removal of DMTr and DMF groups, 5′ monophosphorylation, imidazolide formation, diphosphorylation, and regioselective m 7 methylation. The final coupling reaction of m 7(LNA) GDP with ImGMP in the presence of zinc chloride as a catalyst affords m 7(LNA) G[5′]ppp[5′]G in 59% yield. © 2021 Wiley Periodicals LLC. This article was corrected on 18 July 2022. See the end of the full text for details. Basic Protocol : Synthesis of an LNA‐substituted dinucleotide cap analog Support Protocol : Preparation of the tris(tributylammonium) phosphate linker