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Activity-Based Probes for Proteases Pave the Way to Theranostic Applications

Proteases are important enzymes in health and disease. Their activities are regulated at multiple levels. In fact, proteases are synthesized as inactive proenzymes (zymogens) that are activated by proteolytic removal of their pro-peptide sequence and can remain active or their activity can be attenu...

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Autores principales: Sotiropoulou, Georgia, Zingkou, Eleni, Bisyris, Evangelos, Pampalakis, Georgios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145445/
https://www.ncbi.nlm.nih.gov/pubmed/35631563
http://dx.doi.org/10.3390/pharmaceutics14050977
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author Sotiropoulou, Georgia
Zingkou, Eleni
Bisyris, Evangelos
Pampalakis, Georgios
author_facet Sotiropoulou, Georgia
Zingkou, Eleni
Bisyris, Evangelos
Pampalakis, Georgios
author_sort Sotiropoulou, Georgia
collection PubMed
description Proteases are important enzymes in health and disease. Their activities are regulated at multiple levels. In fact, proteases are synthesized as inactive proenzymes (zymogens) that are activated by proteolytic removal of their pro-peptide sequence and can remain active or their activity can be attenuated by complex formation with specific endogenous inhibitors or by limited proteolysis or degradation. Consequently, quite often, only a fraction of the protease molecules is in the active/functional form, thus, the abundance of a protease is not always linearly proportional to the (patho)physiological function(s). Therefore, assays to determine the active forms of proteases are needed, not only in research but also in molecular diagnosis and therapy. Activity-based probes (ABPs) are chemical entities that bind covalently to the active enzyme/protease. ABPs carry a detection tag to enable localization and quantification of specific enzymatic/proteolytic activities with applications in molecular imaging and diagnosis. Moreover, ABPs act as suicide inhibitors of proteases, which can be exploited for delineation of the functional role(s) of a given protease in (patho) biological context and as potential therapeutics. In this sense, ABPs represent new theranostic agents. We outline recent developments pertaining to ABPs for proteases with potential therapeutic applications, with the aim to highlight their importance in theranostics.
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spelling pubmed-91454452022-05-29 Activity-Based Probes for Proteases Pave the Way to Theranostic Applications Sotiropoulou, Georgia Zingkou, Eleni Bisyris, Evangelos Pampalakis, Georgios Pharmaceutics Review Proteases are important enzymes in health and disease. Their activities are regulated at multiple levels. In fact, proteases are synthesized as inactive proenzymes (zymogens) that are activated by proteolytic removal of their pro-peptide sequence and can remain active or their activity can be attenuated by complex formation with specific endogenous inhibitors or by limited proteolysis or degradation. Consequently, quite often, only a fraction of the protease molecules is in the active/functional form, thus, the abundance of a protease is not always linearly proportional to the (patho)physiological function(s). Therefore, assays to determine the active forms of proteases are needed, not only in research but also in molecular diagnosis and therapy. Activity-based probes (ABPs) are chemical entities that bind covalently to the active enzyme/protease. ABPs carry a detection tag to enable localization and quantification of specific enzymatic/proteolytic activities with applications in molecular imaging and diagnosis. Moreover, ABPs act as suicide inhibitors of proteases, which can be exploited for delineation of the functional role(s) of a given protease in (patho) biological context and as potential therapeutics. In this sense, ABPs represent new theranostic agents. We outline recent developments pertaining to ABPs for proteases with potential therapeutic applications, with the aim to highlight their importance in theranostics. MDPI 2022-04-30 /pmc/articles/PMC9145445/ /pubmed/35631563 http://dx.doi.org/10.3390/pharmaceutics14050977 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sotiropoulou, Georgia
Zingkou, Eleni
Bisyris, Evangelos
Pampalakis, Georgios
Activity-Based Probes for Proteases Pave the Way to Theranostic Applications
title Activity-Based Probes for Proteases Pave the Way to Theranostic Applications
title_full Activity-Based Probes for Proteases Pave the Way to Theranostic Applications
title_fullStr Activity-Based Probes for Proteases Pave the Way to Theranostic Applications
title_full_unstemmed Activity-Based Probes for Proteases Pave the Way to Theranostic Applications
title_short Activity-Based Probes for Proteases Pave the Way to Theranostic Applications
title_sort activity-based probes for proteases pave the way to theranostic applications
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145445/
https://www.ncbi.nlm.nih.gov/pubmed/35631563
http://dx.doi.org/10.3390/pharmaceutics14050977
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