Visualization of membrane localization and the functional state of CB<sub>2</sub>R pools using matched agonist and inverse agonist probe pairs

doi:10.1039/d4sc00402g

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	Visualization of membrane localization and the functional state of CB₂R pools using matched agonist and inverse agonist probe pairs
	Wasinska-Kalwa, M.1; Omran, A.1; Mach, L.1; Scipioni, L.3,10; Bouma, J.2; Li, X.4,5 ; Radetzki, S.1; Mostinski, Y.1; Schippers, M.6; Gazzi, T.1; van der Horst, C.2; Brennecke, B.1; Hanske, A.1; Kolomeets, Y.1; Guba, W.6; Sykes, D.7,8; von Kries, J. P.1; Broichhagen, J.1; Hua, T.4,5 ; Veprintsev, D.7,8; Heitman, L. H.2; Oddi, S.9,10; MacCarrone, M.3,10; Grether, U.6; Nazare, M.1
	2024-10-01
发表期刊	CHEMICAL SCIENCE (IF:7.6[JCR-2023],8.0[5-Year])
ISSN	2041-6520
EISSN	2041-6539
卷号	15 期号:44 页码:18443-18454
发表状态	已发表
DOI	10.1039/d4sc00402g
摘要	The diversity of physiological roles of the endocannabinoid system has turned it into an attractive yet elusive therapeutic target. However, chemical probes with various functionalities could pave the way for a better understanding of the endocannabinoid system at the cellular level. Notably, inverse agonists of CB2R - a key receptor of the endocannabinoid system - lagged behind despite the evidence regarding the therapeutic potential of its antagonism. Herein, we report a matched fluorescent probe pair based on a common chemotype to address and visualize both the active and inactive states of CB2R, selectively. Alongside extensive cross-validation by flow cytometry, time-lapse confocal microscopy, and super-resolution microscopy, we successfully visualize the intracellular localization of CB2R pools in live cells. The synthetic simplicity, together with the high CB2R-selectivity and specificity of our probes, turns them into valuable tools in chemical biology and drug development that can benefit the clinical translatability of CB2R-based drugs.
关键词	Confocal microscopy Flow cytometry Cellular levels Chemical probes Endocannabinoid Fluorescent probes Functional state Inverse agonists Membrane localization Physiological roles Therapeutic potentials Therapeutic targets
URL	查看原文
收录类别	SCI ; EI
语种	英语
资助项目	European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS[PNRR-MAD-2022-12376730] ; EU-OPENSCREEN-DRIVE (Ensuring long-term sustainability of excellence in chemical biology within Europe and beyond) grant[823893]
WOS研究方向	Chemistry
WOS类目	Chemistry, Multidisciplinary
WOS记录号	WOS:001334834500001
出版者	ROYAL SOC CHEMISTRY
EI入藏号	20244417287179
EI主题词	Probes
EI分类号	1301.3.1 ; 746 Imaging Techniques ; 941.2 Acoustic Variables Measurements
原始文献类型	Article in Press
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/439485
专题	iHuman研究所生命科学与技术学院生命科学与技术学院_硕士生 iHuman研究所_PI研究组_华甜组
通讯作者	Oddi, S.; MacCarrone, M.; Grether, U.; Nazare, M.
作者单位	1.Leibniz Forschungsinst Mol Pharmakol FMP, Campus Berlin Buch, D-13125 Berlin, Germany 2.Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, NL-2333 CC Leiden, Netherlands 3.Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy 4.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, CH-4070 Basel, Switzerland 7.Univ Nottingham, Sch Life Sci, Div Physiol Pharmacol & Neurosci, Nottingham NG7 2UH, England 8.Univ Birmingham, Univ Nottingham, Ctr Membrane Prot & Receptors COMPARE, Midlands, England 9.Univ Teramo, Dept Vet Med, Via R Balzarini 1, I-64100 Teramo, Italy 10.Santa Lucia Fdn, Inst Res & Hlth Care IRCCS, European Ctr Brain Res, Via Fosso Fiorano 64, I-00143 Rome, Italy
推荐引用方式 GB/T 7714	Wasinska-Kalwa, M.,Omran, A.,Mach, L.,et al. Visualization of membrane localization and the functional state of CB₂R pools using matched agonist and inverse agonist probe pairs[J]. CHEMICAL SCIENCE,2024,15(44):18443-18454.
APA	Wasinska-Kalwa, M..,Omran, A..,Mach, L..,Scipioni, L..,Bouma, J..,...&Nazare, M..(2024).Visualization of membrane localization and the functional state of CB₂R pools using matched agonist and inverse agonist probe pairs.CHEMICAL SCIENCE,15(44),18443-18454.
MLA	Wasinska-Kalwa, M.,et al."Visualization of membrane localization and the functional state of CB₂R pools using matched agonist and inverse agonist probe pairs".CHEMICAL SCIENCE 15.44(2024):18443-18454.