Orthophosphoric Acid Coated Cell Membrane Array for GPCR Binding

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Solution Overview

Problem

Current cell membrane arrays for analyzing G protein-coupled receptor (GPCR) interactions suffer from high non-specific binding, which hampers accurate quantification of ligand-receptor interactions and intracellular signaling mechanisms.

Innovation Solution

A cell membrane array coated with orthophosphoric acid, containing microdeposits of cell membrane preparations, where unlabeled candidate compounds interact with labeled GTP or its non-hydrolyzable analog, allowing specific binding quantification through washing and signal measurement, thereby reducing non-specific binding and enhancing accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If cell membrane arrays are used for analyzing GPCR interactions, then the ability to analyze ligand-receptor interactions is improved, but non-specific binding increases reducing accuracy

Engineering Contradiction:
Improveability to analyze ligand-receptor interactionsVSAvoidaccuracy of quantification
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent introduces an intermediary substance (exogenous G protein or G protein subunit) that mediates between the GPCR and the detection system. This intermediary allows specific detection of GPCR activation while reducing non-specific binding to the membrane array surface, thereby improving measurement precision without sacrificing analytical capability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical or physical parameters of the membrane array surface by coating with specific materials or modifying surface properties. This parameter change reduces non-specific binding sites while preserving specific GPCR-G protein interaction sites, thus improving accuracy of quantification

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The method effectively quantifies GPCR-G protein binding and intracellular signaling, providing a more precise analysis of ligand-receptor interactions and their effects on second messengers, improving the accuracy of drug development and therapeutic target identification.

Implementation Method 1

putting an unlabeled candidate compound in contact with a cell membrane array in the presence of labeled GTP or of a labeled, non-hydrolyzable analog thereof, in conditions allowing the interaction between said compound and said GPCR present in said cell membranes, and between said labeled GTP or analog thereof and said G protein also present in said cell membranes

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Data Source

PatentEP1930727B1Method of quantifying the g protein-coupled receptor (GPCR)/g protein coupling using a cell membrane array
Publication Date: 2013.04.17 UNIV DEL PAIS VASCO EUSKAL HERRIKO UNIBERTSITATEA
  • EP1930727B1 patent drawingFigure 1~2
  • EP1930727B1 patent drawingFigure 3A~3B
  • EP1930727B1 patent drawingFigure 4

AI summary

The invention relates to a method for quantifying G protein-coupled receptor (GPCR)-G protein binding by means of using a cell membrane array, which comprises (i) putting an unlabeled candidate compound in contact with a cell membrane array in the presence of labeled GTP or of a labeled, non-hydrolyzable analog thereof, in conditions allowing the interaction between said compound and said GPCR present in said cell membranes, and between said labeled GTP or analog thereof and said G protein present in said membranes; (ii) washing; and (iii) quantifying the signal obtained due to the binding of the labeled GTP (or analog) to said G protein. It is applicable in the analysis of the interaction between compounds and cell membrane receptor proteins and of the intracellular signaling mechanisms triggering this interaction mechanism mediated by said compounds.