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Stereoretentive Post-Translational Protein Editing
[Image: see text] Chemical post-translational methods allow convergent side-chain editing of proteins without needing to resort to genetic intervention. Current approaches that allow the creation of constitutionally native side chains via C–C bond formation, using off-protein carbon-centered C· radi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037454/ https://www.ncbi.nlm.nih.gov/pubmed/36968537 http://dx.doi.org/10.1021/acscentsci.2c00991 |
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author | Fu, Xia-Ping Yuan, Yizhi Jha, Ajay Levin, Nikita Giltrap, Andrew M. Ren, Jack Mamalis, Dimitrios Mohammed, Shabaz Davis, Benjamin G. |
author_facet | Fu, Xia-Ping Yuan, Yizhi Jha, Ajay Levin, Nikita Giltrap, Andrew M. Ren, Jack Mamalis, Dimitrios Mohammed, Shabaz Davis, Benjamin G. |
author_sort | Fu, Xia-Ping |
collection | PubMed |
description | [Image: see text] Chemical post-translational methods allow convergent side-chain editing of proteins without needing to resort to genetic intervention. Current approaches that allow the creation of constitutionally native side chains via C–C bond formation, using off-protein carbon-centered C· radicals added to unnatural amino acid radical acceptor (SOMOphile, singly occupied molecular orbital (SOMO)) “tags” such as dehydroalanine, are benign and wide-ranging. However, they also typically create epimeric mixtures of d/l-residues. Here, we describe a light-mediated desulfurative method that, through the creation and reaction of stereoretained on-proteinl-alanyl C(β)· radicals, allows C(β)–H(γ), C(β)–O(γ), C(β)–Se(γ), C(β)–B(γ), and C(β)–C(γ) bond formation to flexibly generate site-selectively edited proteins with full retention of native stereochemistry under mild conditions from a natural amino acid precursor. This methodology shows great potential to explore protein side-chain diversity and function and in the construction of useful bioconjugates. |
format | Online Article Text |
id | pubmed-10037454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-100374542023-03-25 Stereoretentive Post-Translational Protein Editing Fu, Xia-Ping Yuan, Yizhi Jha, Ajay Levin, Nikita Giltrap, Andrew M. Ren, Jack Mamalis, Dimitrios Mohammed, Shabaz Davis, Benjamin G. ACS Cent Sci [Image: see text] Chemical post-translational methods allow convergent side-chain editing of proteins without needing to resort to genetic intervention. Current approaches that allow the creation of constitutionally native side chains via C–C bond formation, using off-protein carbon-centered C· radicals added to unnatural amino acid radical acceptor (SOMOphile, singly occupied molecular orbital (SOMO)) “tags” such as dehydroalanine, are benign and wide-ranging. However, they also typically create epimeric mixtures of d/l-residues. Here, we describe a light-mediated desulfurative method that, through the creation and reaction of stereoretained on-proteinl-alanyl C(β)· radicals, allows C(β)–H(γ), C(β)–O(γ), C(β)–Se(γ), C(β)–B(γ), and C(β)–C(γ) bond formation to flexibly generate site-selectively edited proteins with full retention of native stereochemistry under mild conditions from a natural amino acid precursor. This methodology shows great potential to explore protein side-chain diversity and function and in the construction of useful bioconjugates. American Chemical Society 2023-02-24 /pmc/articles/PMC10037454/ /pubmed/36968537 http://dx.doi.org/10.1021/acscentsci.2c00991 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 | Fu, Xia-Ping Yuan, Yizhi Jha, Ajay Levin, Nikita Giltrap, Andrew M. Ren, Jack Mamalis, Dimitrios Mohammed, Shabaz Davis, Benjamin G. Stereoretentive Post-Translational Protein Editing |
title | Stereoretentive Post-Translational Protein Editing |
title_full | Stereoretentive Post-Translational Protein Editing |
title_fullStr | Stereoretentive Post-Translational Protein Editing |
title_full_unstemmed | Stereoretentive Post-Translational Protein Editing |
title_short | Stereoretentive Post-Translational Protein Editing |
title_sort | stereoretentive post-translational protein editing |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037454/ https://www.ncbi.nlm.nih.gov/pubmed/36968537 http://dx.doi.org/10.1021/acscentsci.2c00991 |
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