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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...

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Autores principales: Fu, Xia-Ping, Yuan, Yizhi, Jha, Ajay, Levin, Nikita, Giltrap, Andrew M., Ren, Jack, Mamalis, Dimitrios, Mohammed, Shabaz, Davis, Benjamin G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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.
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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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