Modular Synthesis of Ligand-Directed Covalent Probes DOI

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

Covalent functionalization of G protein-coupled receptors by small molecular probes DOI Creative Commons
Bert L. H. Beerkens, Adriaan P. IJzerman, Laura H. Heitman

и другие.

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

0
Fluorescent Tools for Imaging Class A G-protein Coupled Receptors DOI Creative Commons
Renáta Szabó,

Ágnes Hornyánszky,

Dóra Kiss

и другие.

European Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер unknown, С. 107074 - 107074

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
A universal cannabinoid CB1 and CB2 receptor TR-FRET kinetic ligand-binding assay DOI Creative Commons
Leire Borrega‐Román, Bradley L. Hoare, Miroslav Kosar

и другие.

Frontiers 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

0
A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells DOI Creative Commons
Xavier Gómez‐Santacana, Marin Boutonnet,

Carles Martínez-Juvés

и другие.

Communications Chemistry, Год журнала: 2025, Номер 8(1)

Опубликована: Апрель 11, 2025

Язык: Английский

Процитировано

0
In-brain synthesis of receptor-based protease sensors by coupling ligand-directed chemistry and click chemistry DOI Creative Commons
Seiji Sakamoto,

Kazuki Shiraiwa,

Mengchu Wang

и другие.

Nature Synthesis, Год журнала: 2025, Номер unknown

Опубликована: Июнь 2, 2025

Язык: Английский

Процитировано

0
A ClO− triggered phenol derivative that induced mitochondrial damage for tumor therapy DOI

Jiarao Sun,

Wei Chen,

Lingxiu Kong

и другие.

Sensors and Actuators B Chemical, Год журнала: 2024, Номер 409, С. 135619 - 135619

Опубликована: Март 7, 2024

Язык: Английский

Процитировано

1
Activity-Based Acylome Profiling with N-(Cyanomethyl)-N-(phenylsulfonyl)amides for Targeted Lysine Acylation and Post-Translational Control of Protein Function in Cells DOI
Elizabeth M. Ryan,

Michael A. Norinskiy,

Amy K. Bracken

и другие.

Journal 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

1
Rational Design, Synthesis, and Evaluation of Fluorescent CB2 Receptor Ligands for Live-Cell Imaging: A Comprehensive Review DOI Creative Commons
Pinaki Bhattacharjee, Malliga R. Iyer

Pharmaceuticals, Год журнала: 2023, Номер 16(9), С. 1235 - 1235

Опубликована: Авг. 31, 2023

The cannabinoid receptors CB

Язык: Английский

Процитировано

2
Optochemical profiling of receptor-proximal proteins in vivo in minutes DOI Creative Commons
Itaru Hamachi,

Mikiko Takato,

Seiji Sakamoto

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 14, 2023

Abstract Understanding how protein-protein interaction networks in the brain give rise to cognitive functions necessitates their characterization live animals. However, tools available for this purpose require potentially disruptive genetic modifications and lack temporal resolution necessary track rapid changes vivo. Here, we combined ligand-directed chemistry photocatalyzed singlet oxygen generation identify neurotransmitter receptor-proximal proteins mouse using only small-molecule reagents minutes of photoirradiation. Named PhoxID (photooxidation-driven proximity labeling proteome identification), our method not recapitulated known interactomes two endogenous receptors (AMPAR GABAAR) but also uncovered age-dependent shifts, identifying NECTIN3 IGSF3 as developmentally regulated AMPAR-proximal cerebellum. Overall, work establishes a flexible generalizable platform study receptor microenvironments genetically intact specimens with an unprecedented resolution.

Язык: Английский

Процитировано

1
In-brain construction of receptor-based protease sensors by coupling ligand-directed chemistry and click chemistry DOI Open Access
Seiji Sakamoto,

Kazuki Shiraiwa,

Mengchu Wang

и другие.

bioRxiv (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

0