A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study

We present the development of a native chemical ligation handle that also functions as a masked electrophile that can be liberated during synthesis when required. This handle can thus be used for the synthesis of complex activity-based probes. We describe the use of this handle in the generation of...

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Detalles Bibliográficos
Autores principales: Mulder, Monique P C, El Oualid, Farid, ter Beek, Jarno, Ovaa, Huib
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2014
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159580/
https://www.ncbi.nlm.nih.gov/pubmed/24623714
http://dx.doi.org/10.1002/cbic.201402012
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author Mulder, Monique P C
El Oualid, Farid
ter Beek, Jarno
Ovaa, Huib
author_facet Mulder, Monique P C
El Oualid, Farid
ter Beek, Jarno
Ovaa, Huib
author_sort Mulder, Monique P C
collection PubMed
description We present the development of a native chemical ligation handle that also functions as a masked electrophile that can be liberated during synthesis when required. This handle can thus be used for the synthesis of complex activity-based probes. We describe the use of this handle in the generation of linkage-specific activity-based deubiquitylating enzyme probes that contain substrate context and closely mimic the native ubiquitin isopeptide linkage. We have generated activity-based probes based on all seven isopeptide-linked diubiquitin topoisomers and demonstrated their structural integrity and ability to label DUBs in a linkage-specific manner.
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spelling pubmed-41595802014-09-22 A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study Mulder, Monique P C El Oualid, Farid ter Beek, Jarno Ovaa, Huib Chembiochem Communications We present the development of a native chemical ligation handle that also functions as a masked electrophile that can be liberated during synthesis when required. This handle can thus be used for the synthesis of complex activity-based probes. We describe the use of this handle in the generation of linkage-specific activity-based deubiquitylating enzyme probes that contain substrate context and closely mimic the native ubiquitin isopeptide linkage. We have generated activity-based probes based on all seven isopeptide-linked diubiquitin topoisomers and demonstrated their structural integrity and ability to label DUBs in a linkage-specific manner. WILEY-VCH Verlag 2014-05-05 2014-03-12 /pmc/articles/PMC4159580/ /pubmed/24623714 http://dx.doi.org/10.1002/cbic.201402012 Text en © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. https://creativecommons.org/licenses/by-nc-nd/4.0/ © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Communications
Mulder, Monique P C
El Oualid, Farid
ter Beek, Jarno
Ovaa, Huib
A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study
title A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study
title_full A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study
title_fullStr A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study
title_full_unstemmed A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study
title_short A Native Chemical Ligation Handle that Enables the Synthesis of Advanced Activity-Based Probes: Diubiquitin as a Case Study
title_sort native chemical ligation handle that enables the synthesis of advanced activity-based probes: diubiquitin as a case study
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159580/
https://www.ncbi.nlm.nih.gov/pubmed/24623714
http://dx.doi.org/10.1002/cbic.201402012
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