Macrocyclic Peptide Complex for c-Met Agonist Stability

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Solution Overview

Problem

Current peptide drugs targeting c-Met have limitations in stability and specificity, which hampers their effectiveness as both anticancer agents and regenerative therapy tools due to rapid degradation and low protease resistance.

Innovation Solution

A macrocyclic peptide complex is developed that binds to c-Met, promoting autophosphorylation and activating the c-Met signaling pathway, enhancing cell growth and migration, thereby improving stability and specificity through multimerization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If peptide drugs are used to target c-Met, then specificity and physiological activity are improved, but protease resistance and stability are worsened

Engineering Contradiction:
ImprovespecificityVSAvoidprotease resistance
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies macrocyclization to transform linear peptides into cyclic structures, creating a composite molecular architecture that combines the specificity of peptide-drug interactions with the enhanced stability of cyclic structures. This structural transformation provides resistance against proteolytic degradation while maintaining target binding capability

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent modifies the structural parameters of peptides by introducing cyclic constraints through macrocyclization. This parameter change from linear to cyclic configuration fundamentally alters the peptide's resistance to protease degradation while preserving its ability to specifically bind to c-Met target molecules

Inventive Principle:
Principle #35Parameter changes

2Reliability

If peptide drugs are used to target c-Met, then physiological activity is improved, but duration of action is worsened due to rapid degradation

Engineering Contradiction:
Improvephysiological activityVSAvoidduration of action
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent creates a composite molecular structure through macrocyclization that combines the functional advantages of peptide drugs with the stability advantages of cyclic structures, thereby extending the duration of action while maintaining physiological activity

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

By changing the structural parameter from linear to cyclic configuration, the patent extends the metabolic half-life of the peptide drug, thereby increasing its duration of action in the body while preserving its physiological effectiveness

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If macrocyclic peptide complex is used, then stability and specificity are improved, but device complexity is worsened

Engineering Contradiction:
ImprovestabilityVSAvoidcomplexity of peptide complex
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent divides the complex macrocyclic structure into modular repeating units that can be systematically assembled. Each unit contributes to the overall stability and specificity, allowing the complex structure to be constructed from standardized building blocks rather than as a monolithic complex

Inventive Principle:
Principle #1Segmentation

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 peptide complex effectively promotes cell growth and migration, making it suitable for regenerative therapy and organ protection during transplantation, while maintaining stability and specificity.

Implementation Method 1

promotes autophosphorylation of c-Met proteins and activates a c-Met signaling pathway

Methodology Applied
Scientific EffectAutophosphorylation: Chemical Bonding

Data Source

PatentEP3059244B1C-met protein agonist
Publication Date: 2020.08.26 THE UNIV OF TOKYO
  • EP3059244B1 patent drawingFigure 1
  • EP3059244B1 patent drawingFigure 2A
  • EP3059244B1 patent drawingFigure 2B

AI summary

Object of the present invention is to provide a peptide functioning as a c-Met agonist. The present invention provides a peptide complex comprising two or more peptides that bind to a c-Met protein and a linker that links the two or more peptides to one another. Such a peptide complex promotes autophosphorylation of the c-Met protein and induces cell growth.