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Synfacts 2021; 17(12): 1389
DOI: 10.1055/s-0041-1737128
Chemistry in Medicine and Biology

On-Demand Synthesis of Modified Oligonucleotides

Contributor(s):
Dirk Trauner
,
Andrej Shemet
Huang Y, Knouse KW, Qiu S, Hao W, Padial NM, Vantourout JC, Zheng B, Mercer SE, Lopez-Ogalla J, Narayan R, Olson RE, Blackmond DG, Eastgate MD, *, Schmidt MS, *, McDonald IM, *, Baran PS. * Elsie Biotechnologies, San Diego, Bristol Myers Squibb, New Brunswick, Bristol Myers Squibb, Cambridge, and The Scripps Research Institute, La Jolla, USA
A P(V) Platform for Oligonucleotide Synthesis.

Science 2021;
373: 1265-1270
DOI: 10.1126/science.abi9727.
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Key words

P(V) chemistry - phosphate-based linkages - phosphorothioates - phosphorodithioates - phosphate diesters

Significance

Oligonucleotides with unnatural phosphate linkages have emerged as promising drug candidates due to their desirable pharmacological properties. Accordingly, many FDA approvals have been issued for therapeutic oligonucleo­tides in the last years. Their synthesis, however, is challenging using existing methods.


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Comment

Based on the phosphorous sulfur incorporation (PSI or ψ) reagent for the synthesis of optically pure phosphorothioates (Science 2018, 361, 1234), the researchers developed three new reagents for the synthesis of racemic phosphorothioates (rac-ψ), phosphorodithioates (ψ2), and phosphate diester (ψO) linkages.


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Publication History

Article published online:
17 November 2021

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