Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan

[Image: see text] Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms. Herein, we report the photocat...

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Autores principales: Lee, Joanna C., Cuthbertson, James D., Mitchell, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10391624/
https://www.ncbi.nlm.nih.gov/pubmed/37462428
http://dx.doi.org/10.1021/acs.orglett.3c01795
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author Lee, Joanna C.
Cuthbertson, James D.
Mitchell, Nicholas J.
author_facet Lee, Joanna C.
Cuthbertson, James D.
Mitchell, Nicholas J.
author_sort Lee, Joanna C.
collection PubMed
description [Image: see text] Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms. Herein, we report the photocatalytic C2-alkylation of tryptophan using bromodifluoroacetate/acetamide-derived radical precursors. This rapid visible-light-mediated reaction is additive-free, operationally simple, and tolerates diverse functionality. We demonstrate the late-stage modification of a variety of complex peptides, including examples of biological significance.
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spelling pubmed-103916242023-08-02 Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan Lee, Joanna C. Cuthbertson, James D. Mitchell, Nicholas J. Org Lett [Image: see text] Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms. Herein, we report the photocatalytic C2-alkylation of tryptophan using bromodifluoroacetate/acetamide-derived radical precursors. This rapid visible-light-mediated reaction is additive-free, operationally simple, and tolerates diverse functionality. We demonstrate the late-stage modification of a variety of complex peptides, including examples of biological significance. American Chemical Society 2023-07-18 /pmc/articles/PMC10391624/ /pubmed/37462428 http://dx.doi.org/10.1021/acs.orglett.3c01795 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Lee, Joanna C.
Cuthbertson, James D.
Mitchell, Nicholas J.
Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan
title Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan
title_full Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan
title_fullStr Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan
title_full_unstemmed Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan
title_short Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan
title_sort chemoselective late-stage functionalization of peptides via photocatalytic c2-alkylation of tryptophan
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10391624/
https://www.ncbi.nlm.nih.gov/pubmed/37462428
http://dx.doi.org/10.1021/acs.orglett.3c01795
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AT mitchellnicholasj chemoselectivelatestagefunctionalizationofpeptidesviaphotocatalyticc2alkylationoftryptophan

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