T1R Taste Receptor Assay Counter-Screening for False Positives

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Solution Overview

Problem

Existing assays for identifying compounds that modulate sweet or umami taste using T1R2/T1R3 and T1R1/T1R3 receptors often produce false positives, which do not elicit the desired taste effects in humans, due to non-physiologically relevant interactions.

Innovation Solution

Incorporating a counter-screen using homomeric T1R2 or T1R1 assays to identify compounds that bind to or modulate the activity of homomeric T1R2 or T1R1, respectively, to eliminate false positives by assessing their effectiveness in human taste tests.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If heteromeric T1R2/T1R3 or T1R1/T1R3 receptor assays are used to screen for taste-modulating compounds, then the ability to identify potential sweet or umami taste modulators is improved, but the number of false positives increases due to non-physiologically relevant interactions

Engineering Contradiction:

Improveability to identify taste modulatorsVSAvoidaccuracy of taste modulation prediction

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The screening process is divided into two separate assays: a primary heteromeric T1R2/T1R3 or T1R1/T1R3 receptor assay to identify potential taste modulators, and a secondary homomeric T1R2 or T1R1 receptor counter-screen to eliminate false positives. This segmentation allows each assay to serve a specific function, improving both the ability to identify candidates and the reliability of predictions.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The homomeric T1R2 or T1R1 receptor assay acts as an intermediary counter-screen between the primary heteromeric receptor assay and final compound selection. This intermediate step filters out compounds that bind to homomeric receptors but not to the physiologically relevant heteromeric receptors, thereby eliminating false positives while preserving true candidates.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If a counter-screen using homomeric T1R2 or T1R1 assays is incorporated to eliminate false positives, then the reliability of compound identification is improved, but the complexity of the screening process increases

Engineering Contradiction:

Improveaccuracy of taste modulation predictionVSAvoidscreening process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The complex screening process is segmented into two distinct, modular assays that can be performed sequentially. The first assay screens for potential taste modulators using heteromeric receptors, and the second assay counterscreens using homomeric receptors. This modular segmentation makes the overall complex process more manageable and systematically organized.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The homomeric receptor counter-screen is performed as a preliminary action before final compound selection and testing. By conducting this filtering step early in the screening process, false positives are eliminated before resources are invested in further development and testing of non-viable candidates, thereby improving reliability while managing complexity through early elimination.

Inventive Principle:

Principle #10Preliminary action

3Productivity

If high throughput screening format is used to screen hundreds of compounds, then the productivity of compound identification is improved, but the difficulty of eliminating false positives increases

Engineering Contradiction:

Improvenumber of compounds screenedVSAvoidfalse positive identification

Core Design Contradiction:

ProductivityVSDifficulty of detecting and measuring

Solution Approach 1:

The high throughput screening process is segmented into two separate high-throughput assays: a primary screen using heteromeric T1R2/T1R3 or T1R1/T1R3 receptors and a counter-screen using homomeric T1R2 or T1R1 receptors. Both assays can be performed in high throughput format, allowing hundreds of compounds to be screened efficiently while maintaining the ability to detect and eliminate false positives through the systematic comparison of results from both assays.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS10281467B2Screening assays to identify compounds which modulate T1R associated taste modalities which eliminate false positives

Publication Date: 2019.05.07 FIRMENICH INC

AI summary

This invention relates to assays which screen for compounds that modulate taste elicited by the T1R2/T1R3 sweet taste receptor which include a novel counter screen to eliminate false positives. In addition, the invention contemplates assays which screen for compounds that modulate taste elicited by the T1R1/T1R3 umami taste receptor which include a novel counter screen to eliminate false positives. Preferably the assays are conducted in high throughput format thereby enabling the screening of many hundreds of different compounds whereby the counter screen significantly improves assay efficiency. Further, the invention relates to the use of the compounds identified in the subject screening assays to modulate T1R associated taste perception.