Development of Fluorescent and Biotin Probes Targeting NLRP3
Extracellular signals drive the nucleation of the NLRP3 inflammasome which leads to the release of cytokines and causes inflammatory events. Hence, the inflammasome has gained enormous momentum in biomedical basic research. The detailed mechanisms of inflammasome generation and regulation remain to...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2021.642273/full |
| _version_ | 1828932211160645632 |
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| author | Tim Keuler Karl Gatterdam Anil Akbal Marta Lovotti Michael Marleaux Matthias Geyer Eicke Latz Michael Gütschow |
| author_facet | Tim Keuler Karl Gatterdam Anil Akbal Marta Lovotti Michael Marleaux Matthias Geyer Eicke Latz Michael Gütschow |
| author_sort | Tim Keuler |
| collection | DOAJ |
| description | Extracellular signals drive the nucleation of the NLRP3 inflammasome which leads to the release of cytokines and causes inflammatory events. Hence, the inflammasome has gained enormous momentum in biomedical basic research. The detailed mechanisms of inflammasome generation and regulation remain to be elucidated. Our study was directed toward the design, convergent synthesis, and initial biochemical evaluation of activity-based probes addressing NLRP3. For this purpose, probes were assembled from a CRID3/MCC950-related NLRP3-binding unit, a linker portion and a coumarin 343 fluorophore or biotin. The affinity of our probes to NLRP3 was demonstrated through SPR measurements and their cellular activity was confirmed by reduction of the interleukin 1β release from stimulated bone marrow-derived macrophages. The initial characterizations of NLRP3-targeting probes highlighted the coumarin probe 2 as a suitable tool compound for the cellular and biochemical analysis of the NLRP3 inflammasome. |
| first_indexed | 2024-12-14T00:58:09Z |
| format | Article |
| id | doaj.art-060eff53c04e4d01a5529a0937ec15ac |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-14T00:58:09Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-060eff53c04e4d01a5529a0937ec15ac2022-12-21T23:23:24ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-04-01910.3389/fchem.2021.642273642273Development of Fluorescent and Biotin Probes Targeting NLRP3Tim Keuler0Karl Gatterdam1Anil Akbal2Marta Lovotti3Michael Marleaux4Matthias Geyer5Eicke Latz6Michael Gütschow7Pharmaceutical Institute, University of Bonn, Bonn, GermanyInstitute of Structural Biology, University of Bonn, Bonn, GermanyInstitute of Innate Immunity, University of Bonn, Bonn, GermanyInstitute of Innate Immunity, University of Bonn, Bonn, GermanyInstitute of Structural Biology, University of Bonn, Bonn, GermanyInstitute of Structural Biology, University of Bonn, Bonn, GermanyInstitute of Innate Immunity, University of Bonn, Bonn, GermanyPharmaceutical Institute, University of Bonn, Bonn, GermanyExtracellular signals drive the nucleation of the NLRP3 inflammasome which leads to the release of cytokines and causes inflammatory events. Hence, the inflammasome has gained enormous momentum in biomedical basic research. The detailed mechanisms of inflammasome generation and regulation remain to be elucidated. Our study was directed toward the design, convergent synthesis, and initial biochemical evaluation of activity-based probes addressing NLRP3. For this purpose, probes were assembled from a CRID3/MCC950-related NLRP3-binding unit, a linker portion and a coumarin 343 fluorophore or biotin. The affinity of our probes to NLRP3 was demonstrated through SPR measurements and their cellular activity was confirmed by reduction of the interleukin 1β release from stimulated bone marrow-derived macrophages. The initial characterizations of NLRP3-targeting probes highlighted the coumarin probe 2 as a suitable tool compound for the cellular and biochemical analysis of the NLRP3 inflammasome.https://www.frontiersin.org/articles/10.3389/fchem.2021.642273/fullNLRP3probessurface plasmon resonanceinflammasomeCRID3MCC950 |
| spellingShingle | Tim Keuler Karl Gatterdam Anil Akbal Marta Lovotti Michael Marleaux Matthias Geyer Eicke Latz Michael Gütschow Development of Fluorescent and Biotin Probes Targeting NLRP3 Frontiers in Chemistry NLRP3 probes surface plasmon resonance inflammasome CRID3 MCC950 |
| title | Development of Fluorescent and Biotin Probes Targeting NLRP3 |
| title_full | Development of Fluorescent and Biotin Probes Targeting NLRP3 |
| title_fullStr | Development of Fluorescent and Biotin Probes Targeting NLRP3 |
| title_full_unstemmed | Development of Fluorescent and Biotin Probes Targeting NLRP3 |
| title_short | Development of Fluorescent and Biotin Probes Targeting NLRP3 |
| title_sort | development of fluorescent and biotin probes targeting nlrp3 |
| topic | NLRP3 probes surface plasmon resonance inflammasome CRID3 MCC950 |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2021.642273/full |
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