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Diazo compounds for the bioreversible esterification of proteins

A diazo compound is shown to convert carboxylic acids to esters efficiently in an aqueous environment. The basicity of the diazo compound is critical: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The e...

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Autores principales: McGrath, Nicholas A., Andersen, Kristen A., Davis, Amy K. F., Lomax, Jo E., Raines, Ronald T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275067/
https://www.ncbi.nlm.nih.gov/pubmed/25544883
http://dx.doi.org/10.1039/c4sc01768d
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author McGrath, Nicholas A.
Andersen, Kristen A.
Davis, Amy K. F.
Lomax, Jo E.
Raines, Ronald T.
author_facet McGrath, Nicholas A.
Andersen, Kristen A.
Davis, Amy K. F.
Lomax, Jo E.
Raines, Ronald T.
author_sort McGrath, Nicholas A.
collection PubMed
description A diazo compound is shown to convert carboxylic acids to esters efficiently in an aqueous environment. The basicity of the diazo compound is critical: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chemical modification could enable the key advantages of prodrugs to be translated from small-molecules to proteins.
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spelling pubmed-42750672016-01-01 Diazo compounds for the bioreversible esterification of proteins McGrath, Nicholas A. Andersen, Kristen A. Davis, Amy K. F. Lomax, Jo E. Raines, Ronald T. Chem Sci Chemistry A diazo compound is shown to convert carboxylic acids to esters efficiently in an aqueous environment. The basicity of the diazo compound is critical: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chemical modification could enable the key advantages of prodrugs to be translated from small-molecules to proteins. Royal Society of Chemistry 2015-01-01 2014-10-01 /pmc/articles/PMC4275067/ /pubmed/25544883 http://dx.doi.org/10.1039/c4sc01768d Text en This journal is © The Royal Society of Chemistry 2014 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
McGrath, Nicholas A.
Andersen, Kristen A.
Davis, Amy K. F.
Lomax, Jo E.
Raines, Ronald T.
Diazo compounds for the bioreversible esterification of proteins
title Diazo compounds for the bioreversible esterification of proteins
title_full Diazo compounds for the bioreversible esterification of proteins
title_fullStr Diazo compounds for the bioreversible esterification of proteins
title_full_unstemmed Diazo compounds for the bioreversible esterification of proteins
title_short Diazo compounds for the bioreversible esterification of proteins
title_sort diazo compounds for the bioreversible esterification of proteins
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275067/
https://www.ncbi.nlm.nih.gov/pubmed/25544883
http://dx.doi.org/10.1039/c4sc01768d
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