Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe
This journal is © The Royal Society of Chemistry..
Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Chemical science - 13(2022), 19 vom: 18. Mai, Seite 5539-5545 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gazzi, Thais [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 16.07.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1039/d1sc06659e |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM342159933 |
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| 245 | 1 | 0 | |a Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe |
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| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a This journal is © The Royal Society of Chemistry. | ||
| 520 | |a Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Brennecke, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Atz, Kenneth |e verfasserin |4 aut | |
| 700 | 1 | |a Korn, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Sykes, David |e verfasserin |4 aut | |
| 700 | 1 | |a Forn-Cuni, Gabriel |e verfasserin |4 aut | |
| 700 | 1 | |a Pfaff, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Sarott, Roman C |e verfasserin |4 aut | |
| 700 | 1 | |a Westphal, Matthias V |e verfasserin |4 aut | |
| 700 | 1 | |a Mostinski, Yelena |e verfasserin |4 aut | |
| 700 | 1 | |a Mach, Leonard |e verfasserin |4 aut | |
| 700 | 1 | |a Wasinska-Kalwa, Malgorzata |e verfasserin |4 aut | |
| 700 | 1 | |a Weise, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Hoare, Bradley L |e verfasserin |4 aut | |
| 700 | 1 | |a Miljuš, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Mexi, Maira |e verfasserin |4 aut | |
| 700 | 1 | |a Roth, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Koers, Eline J |e verfasserin |4 aut | |
| 700 | 1 | |a Guba, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Alker, André |e verfasserin |4 aut | |
| 700 | 1 | |a Rufer, Arne C |e verfasserin |4 aut | |
| 700 | 1 | |a Kusznir, Eric A |e verfasserin |4 aut | |
| 700 | 1 | |a Huber, Sylwia |e verfasserin |4 aut | |
| 700 | 1 | |a Raposo, Catarina |e verfasserin |4 aut | |
| 700 | 1 | |a Zirwes, Elisabeth A |e verfasserin |4 aut | |
| 700 | 1 | |a Osterwald, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a Pavlovic, Anto |e verfasserin |4 aut | |
| 700 | 1 | |a Moes, Svenja |e verfasserin |4 aut | |
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| 700 | 1 | |a Nettekoven, Matthias |e verfasserin |4 aut | |
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