Nature Chose Phosphates and Chemists Should Too: How Emerging P(V) Methods Can Augment Existing Strategies.

Autor:	Knouse KW; Elsie Biotechnologies, 4955 Directors Place, San Diego, California 92121, United States.; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Flood DT; Elsie Biotechnologies, 4955 Directors Place, San Diego, California 92121, United States.; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Vantourout JC; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Schmidt MA; Chemical and Synthetic Development, Bristol Myers Squibb, One Squibb Drive, New Brunswick, New Jersey 08903, United States., Mcdonald IM; Small Molecule Drug Discovery, Bristol Myers Squibb, 100 Binney Street, Cambridge, Massachusetts 02142, United States., Eastgate MD; Chemical and Synthetic Development, Bristol Myers Squibb, One Squibb Drive, New Brunswick, New Jersey 08903, United States., Baran PS; Elsie Biotechnologies, 4955 Directors Place, San Diego, California 92121, United States.; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Jazyk:	angličtina
Zdroj:	ACS central science [ACS Cent Sci] 2021 Sep 22; Vol. 7 (9), pp. 1473-1485. Date of Electronic Publication: 2021 Sep 10.
DOI:	10.1021/acscentsci.1c00487
Abstrakt:	Phosphate linkages govern life as we know it. Their unique properties provide the foundation for many natural systems from cell biology and biosynthesis to the backbone of nucleic acids. Phosphates are ideal natural moieties; existing as ionized species in a stable P(V)-oxidation state, they are endowed with high stability but exhibit enzymatically unlockable potential. Despite intense interest in phosphorus catalysis and condensation chemistry, organic chemistry has not fully embraced the potential of P(V) reagents. To be sure, within the world of chemical oligonucleotide synthesis, modern approaches utilize P(III) reagent systems to create phosphate linkages and their analogs. In this Outlook, we present recent studies from our laboratories suggesting that numerous exciting opportunities for P(V) chemistry exist at the nexus of organic synthesis and biochemistry. Applications to the synthesis of stereopure antisense oligonucleotides, cyclic dinucleotides, methylphosphonates, and phosphines are reviewed as well as chemoselective modification to peptides, proteins, and nucleic acids. Finally, an outlook into what may be possible in the future with P(V) chemistry is previewed, suggesting these examples represent just the tip of the iceberg. Competing Interests: The authors declare the following competing financial interest(s): Three of the authors are co-founders of Elsie Biotechnologies, a company that is in the process of licensing some of the technology patented in this outlook. (© 2021 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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