Video Experimental Relacionado
Updated: Nov 2, 2025
07:41
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
9.1K
Agonista alostérico selectivo de un receptor acoplado a la proteína G
Prashant Donthamsetti1, David B Konrad2, Belinda Hetzler3
1Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, United States.
Journal of the American Chemical Society
|June 11, 2021
Resumen
Los investigadores desarrollaron aBINA, un nuevo agonista alostérico con conmutación fotográfica. Este medicamento de precisión activa selectivamente el receptor acoplado a la proteína G 2 (mGluR2) utilizando la luz, ofreciendo un nuevo potencial terapéutico.
Área de la Ciencia:
- Farmacología
- La bioquímica
- Biología molecular
Sus antecedentes:
- Los receptores acoplados a proteínas G (GPCR) son objetivos clave de los fármacos, pero sus similitudes y dinámicas de activación complejas plantean desafíos.
- La fotofarmacología utiliza moléculas activadas por la luz para controlar la acción del medicamento, ofreciendo precisión temporal y espacial.
- Las herramientas fotofarmacológicas existentes incluyen fotoagonistas/antagonistas (no selectivos) y moduladores fotoalostéricos (control indirecto).
Objetivo del estudio:
- Diseñar un agonista alostérico fotointercambiable para el control selectivo y directo de la actividad GPCR.
- Desarrollar una nueva clase de fármacos de precisión para los GPCR y las proteínas de señalización relacionadas.
Principales métodos:
- Incorporación de un azoceno fotoisomerizable en un ligando GPCR para crear una actividad de conmutación de luz.
- Diseño de un modulador alostérico dirigido a un sitio no conservado para una mayor selectividad.
- Desarrollo y prueba de aBINA, un agonista alostérico con conmutación fotográfica para el receptor metabotrópico del glutamato 2 (mGluR2).
Principales resultados:
- Diseño y síntesis exitosas de aBINA, un agonista alostérico fotointercambiable.
- Demostración de que aBINA activa selectivamente el receptor metabotrópico acoplado al Gi/o 2 (mGluR2).
- aBINA proporciona activación directa del receptor tras la estimulación de la luz, independientemente de los ligandos endógenos.
Conclusiones:
- aBINA representa una nueva clase de fármacos de precisión para los GPCR.
- Este enfoque permite un control selectivo y directo basado en la luz sobre la señalización GPCR.
- La tecnología desarrollada es prometedora para el tratamiento de enfermedades que involucran GPCR y otras proteínas de señalización.
Más Videos Relacionados
Videos de Conceptos Relacionados
01:22Activation and Inactivation of G Proteins
8.2K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
8.2K
01:30Transducer Mechanism: G Protein–Coupled Receptors
3.1K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
3.1K
01:21G-protein Coupled Receptors
126.7K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
126.7K
01:15G Protein-coupled Receptors
14.5K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
14.5K
01:12GPCR Desensitization
7.0K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
7.0K
01:29The Two-State Receptor Model
2.7K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
2.7K