Synfacts, Год журнала: 2023, Номер 19(09), С. 0936 - 0936
Опубликована: Авг. 16, 2023
Key words cannabinoid receptor - ligand-directed covalent labeling modular synthesis
Язык: Английский
Synfacts, Год журнала: 2023, Номер 19(09), С. 0936 - 0936
Опубликована: Авг. 16, 2023
Key words cannabinoid receptor - ligand-directed covalent labeling modular synthesis
Язык: Английский
RSC Chemical Biology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
In this review, we take a closer look at the most recent small molecular probes that covalently label G protein-coupled receptors.
Язык: Английский
Процитировано
0European Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер unknown, С. 107074 - 107074
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Апрель 9, 2025
The kinetics of ligand binding to G protein-coupled receptors (GPCRs) is an important optimization parameter in drug discovery. Traditional radioligand assays are labor-intensive, preventing their application at the early stages Fluorescence-based offer several advantages, including a possibility develop homogeneous format, continuous data collection, and higher throughput. This study sought fluorescence-based assay investigate ligand-binding human cannabinoid type 1 2 (CB1R CB2R). We synthesized D77, novel tracer derived from non-selective Δ8-THC. Using time-resolved Förster resonance energy transfer (TR-FRET), we developed physiological temperatures. For CB1R, truncated first 90 amino acids its flexible N-terminal domain reduce FRET distance between terbium cryptate (donor) fluorescent (acceptor). full-length CB2R construct was functional without modification due shorter N-terminus. Motulsky-Mahan competition model used analyze endocannabinoids other non-fluorescent ligands. D77 showed nanomolar-range affinity for CB1R (CB1R91-472) (CB2R1-360), displaying competitive with orthosteric exhibited rapid dissociation both CB2R, which were similar fastest dissociating reference compounds. critical accurately determining on- off-rates measured kinetic properties various agonists antagonists temperature sodium ion concentration. k on values molecules varied by three orders magnitude, slowest (HU308) (rimonabant). A strong correlation observed compounds indicating that association rate primarily determines CB1R. Unlike stronger found constant off suggesting dictate overall CB2R. Exploring parameters candidates could help development programs targeting these receptors.
Язык: Английский
Процитировано
0Communications Chemistry, Год журнала: 2025, Номер 8(1)
Опубликована: Апрель 11, 2025
Язык: Английский
Процитировано
0Nature Synthesis, Год журнала: 2025, Номер unknown
Опубликована: Июнь 2, 2025
Язык: Английский
Процитировано
0Sensors and Actuators B Chemical, Год журнала: 2024, Номер 409, С. 135619 - 135619
Опубликована: Март 7, 2024
Язык: Английский
Процитировано
1Journal of the American Chemical Society, Год журнала: 2024, Номер unknown
Опубликована: Сен. 30, 2024
Lysine acylations are ubiquitous and structurally diverse post-translational modifications that vastly expand the functional heterogeneity of human proteome. Hence, targeted acylation lysine residues has emerged as a strategic approach to exert biomimetic control over protein function. However, existing strategies for in cells often rely on genetic intervention, recruitment endogenous machinery, or nonspecific acylating agents lack methods quantify magnitude specific global level. In this study, we develop activity-based acylome profiling (ABAP), chemoproteomic strategy exploits elaborate
Язык: Английский
Процитировано
1Pharmaceuticals, Год журнала: 2023, Номер 16(9), С. 1235 - 1235
Опубликована: Авг. 31, 2023
The cannabinoid receptors CB
Язык: Английский
Процитировано
2Research Square (Research Square), Год журнала: 2023, Номер unknown
Опубликована: Ноя. 14, 2023
Язык: Английский
Процитировано
1bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 24, 2024
Abstract The chemical modification of natural proteins in living systems is highly desirable toward the cutting-edge research chemistry-biology interface. Recent advances bioorthogonal protein have enabled production chemically functional cultured cell systems. However, few methods are applicable vivo because complexity three-dimensional constructs with diverse, heterogeneous populations and flow filled tissue fluids. Here, we report a genetic engineering-free method to modify receptor various probes mouse brain by combining in-brain ligand-directed chemistry click chemistry, propose guideline for reaction design. rapid selective tethering set fluorescent peptides AMPA-type glutamate receptors (AMPARs) allowed construction receptor-based sensors. These mapping activity matrix metalloproteinase-9 proximal AMPARs be realized high spatial resolution. Our strategy provides new opportunities precise analysis particular microenvironments that has not been able addressed conventional methods. Such should contribute understanding molecular basis complicated events, such as regulation neuroplasticity, most important challenge neuroscience.
Язык: Английский
Процитировано
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