Generation of the UFM1 Toolkit for Profiling UFM1-Specific Proteases and Ligases

Katharina F. Witting; Gerbrand J. Van Der Heden Van Noort; Christian Kofoed; Cami Talavera Ormeño; Dris El Atmioui; Monique P. C. Mulder; Huib Ovaa

doi:10.1002/anie.201809232

Generation of the UFM1 Toolkit for Profiling UFM1-Specific Proteases and Ligases

Katharina F. Witting, Gerbrand J. Van Der Heden Van Noort, Christian Kofoed, Cami Talavera Ormeño, Dris El Atmioui, Monique P. C. Mulder, Huib Ovaa

Kemisk Institut

12 Citationer (Scopus)

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Abstract

Ubiquitin-fold modifier 1 (UFM1) is a reversible post-translational modifier that is covalently attached to target proteins through an enzymatic cascade and removed by designated proteases. Abnormalities in this process, referred to as Ufmylation, have been associated with a variety of human diseases. Given this, the UFM1-specific enzymes represent potential therapeutic targets; however, understanding of their biological function has been hampered by the lack of chemical tools for activity profiling. To address this unmet need, a diversifiable platform for UFM1 activity-based probes (ABPs) utilizing a native chemical ligation (NCL) strategy was developed, enabling the generation of a variety of tools to profile both UFM1 conjugating and deconjugating enzymes. The use of the probes is demonstrated in vitro and in vivo for monitoring UFM1 enzyme reactivity, opening new research avenues.

Originalsprog	Engelsk
Tidsskrift	Angewandte Chemie International Edition
Vol/bind	57
Udgave nummer	43
Sider (fra-til)	14164-14168
Antal sider	5
ISSN	1433-7851
DOI	https://doi.org/10.1002/anie.201809232
Status	Udgivet - 22 okt. 2018

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10.1002/anie.201809232Licens: CC BY-NC-ND

Witting_et_al-2018-Angewandte_Chemie_International_EditionForlagets udgivne version, 2,59 MBLicens: CC BY-NC-ND

Citationsformater

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abstract = "Ubiquitin-fold modifier 1 (UFM1) is a reversible post-translational modifier that is covalently attached to target proteins through an enzymatic cascade and removed by designated proteases. Abnormalities in this process, referred to as Ufmylation, have been associated with a variety of human diseases. Given this, the UFM1-specific enzymes represent potential therapeutic targets; however, understanding of their biological function has been hampered by the lack of chemical tools for activity profiling. To address this unmet need, a diversifiable platform for UFM1 activity-based probes (ABPs) utilizing a native chemical ligation (NCL) strategy was developed, enabling the generation of a variety of tools to profile both UFM1 conjugating and deconjugating enzymes. The use of the probes is demonstrated in vitro and in vivo for monitoring UFM1 enzyme reactivity, opening new research avenues.",

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AU - Witting, Katharina F.

AU - Van Der Heden Van Noort, Gerbrand J.

AU - Kofoed, Christian

AU - Talavera Ormeño, Cami

AU - El Atmioui, Dris

AU - Mulder, Monique P. C.

AU - Ovaa, Huib

PY - 2018/10/22

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N2 - Ubiquitin-fold modifier 1 (UFM1) is a reversible post-translational modifier that is covalently attached to target proteins through an enzymatic cascade and removed by designated proteases. Abnormalities in this process, referred to as Ufmylation, have been associated with a variety of human diseases. Given this, the UFM1-specific enzymes represent potential therapeutic targets; however, understanding of their biological function has been hampered by the lack of chemical tools for activity profiling. To address this unmet need, a diversifiable platform for UFM1 activity-based probes (ABPs) utilizing a native chemical ligation (NCL) strategy was developed, enabling the generation of a variety of tools to profile both UFM1 conjugating and deconjugating enzymes. The use of the probes is demonstrated in vitro and in vivo for monitoring UFM1 enzyme reactivity, opening new research avenues.

AB - Ubiquitin-fold modifier 1 (UFM1) is a reversible post-translational modifier that is covalently attached to target proteins through an enzymatic cascade and removed by designated proteases. Abnormalities in this process, referred to as Ufmylation, have been associated with a variety of human diseases. Given this, the UFM1-specific enzymes represent potential therapeutic targets; however, understanding of their biological function has been hampered by the lack of chemical tools for activity profiling. To address this unmet need, a diversifiable platform for UFM1 activity-based probes (ABPs) utilizing a native chemical ligation (NCL) strategy was developed, enabling the generation of a variety of tools to profile both UFM1 conjugating and deconjugating enzymes. The use of the probes is demonstrated in vitro and in vivo for monitoring UFM1 enzyme reactivity, opening new research avenues.

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JF - Angewandte Chemie International Edition

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ER -

Generation of the UFM1 Toolkit for Profiling UFM1-Specific Proteases and Ligases

Abstract

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