Chemical Zymogens: Specificity and Steroidal Control of Reactivation.
Covalent protein modification
Cysteinome
Enzyme activation
Enzyme chemistry
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
received:
18
04
2023
medline:
2
8
2023
pubmed:
19
4
2023
entrez:
18
4
2023
Statut:
ppublish
Résumé
Activating and masking enzymatic activity on demand is of the highest importance in nature. It is achieved by chemical interconversion of enzymes and the corresponding zymogens through, for example, proteolytic processing or reversible phosphorylation, and affords on-demand activation of enzymes, controlled in space and/or time. In stark contrast, examples of chemical zymogens are very few, and in most cases these are based on disulfide chemistry, which is largely indiscriminate as to the nature of the activating thiol. In this work, we address an outstanding challenge of specificity of reactivation of chemical zymogens. We achieve this through engineering affinity between the chemical zymogen and the activator. Additional, higher-level control over zymogen reactivation is installed in a nature-mimicking approach using steroidal hormones. Taken together, the results of this study take a step towards establishing the specificity of reactivation of synthetic, chemical zymogens. We anticipate that the results of this study will contribute significantly to the development of chemical zymogens as tools for diverse use in chemical biology and biotechnology.
Identifiants
pubmed: 37071475
doi: 10.1002/cbic.202300304
doi:
Substances chimiques
Enzyme Precursors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202300304Informations de copyright
© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.
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