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Lookup NU author(s): Dr Othman AlmusaimiORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Oligonucleotides, comprising single or double strands of RNA or DNA, are vital chemical compounds used in various laboratory and clinical applications. They represent a significant class of therapeutics with a rapidly expanding range of uses. Between 1998 and 2023, 19 oligonucleotides have received approval from the U.S. Food and Drug Administration (FDA). Their synthesis methods have undergone significant evolution over time. This review examines several oligonucleotide synthesis techniques, including phosphodiester, phosphotriester, and phosphoramidite approaches. It begins with a discussion of an early synthesis method involving a phosphoryl chloride intermediate, which proved unstable and prone to hydrolysis. The review then transitions to the solid-phase synthesis method, which uses polymer resins as a solid support, emphasizing its advantages over both phosphotriester and phosphoramidite techniques. This is followed by an exploration of recent advancements in oligonucleotide enzymatic synthesis, concluding with a discussion on modifications to bases, sugars, and backbones designed to improve their properties and therapeutic potential.
Author(s): Al Musaimi O
Publication type: Article
Publication status: Published
Journal: Medicinal Chemistry Research
Year: 2024
Volume: 33
Pages: 2204–2220
Print publication date: 01/12/2024
Online publication date: 21/11/2024
Acceptance date: 05/11/2024
Date deposited: 17/12/2024
ISSN (print): 1054-2523
ISSN (electronic): 1554-8120
Publisher: Springer Nature
URL: https://doi.org/10.1007/s00044-024-03352-7
DOI: 10.1007/s00044-024-03352-7
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