Catalytic Peptide Stability via Box A Segmentation

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Solution Overview

Problem

Current enzyme proteins used for protein degradation are unstable due to environmental factors like humidity, temperature, and acidity, necessitating a more stable catalytic molecule for hydrolysis reactions.

Innovation Solution

A catalytic peptide derived from specific regions of the Tob/BTG protein, including Box A and Box B, with defined amino acid sequences, which catalyzes hydrolysis reactions and exhibits stability across varying conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If enzyme proteins are used to catalyze hydrolysis reactions, then catalytic activity is achieved, but stability under varying environmental conditions deteriorates

Engineering Contradiction:
ImprovestabilityVSAvoidmolecular complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the enzyme protein into smaller peptide segments, specifically identifying that the Box A region (amino acids 2-22 of Tob1) contains the essential catalytic functionality. This segmentation allows the active site to be separated from the rest of the protein structure, creating a stable, minimal peptide catalyst that retains hydrolysis activity while eliminating the instability associated with full enzyme proteins.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent extracts the catalytically active Box A region from the complete Tob1 protein sequence. By isolating and utilizing only this specific 21-amino acid segment (plus flanking regions), the invention removes the portions of the enzyme that are susceptible to denaturation while preserving the hydrolytic function, thereby achieving both stability and catalytic activity.

Inventive Principle:
Principle #2Taking out (Extraction)

2Productivity

If full enzyme proteins are used for catalysis, then complete catalytic function is achieved, but susceptibility to denaturation by humidity, temperature, and acidity increases

Engineering Contradiction:
Improvecatalytic efficiencyVSAvoidenvironmental sensitivity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical parameters of the catalyst by reducing molecular weight from full enzyme protein to minimal peptide. This parameter change fundamentally alters the catalyst's response to environmental factors, making it resistant to denaturation by humidity, temperature, and acidity while maintaining catalytic efficiency through the preserved Box A sequence.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If smaller peptide molecules are used instead of enzyme proteins, then stability improves, but catalytic activity may be reduced

Engineering Contradiction:
ImprovestabilityVSAvoidcatalytic power
Core Design Contradiction:
ReliabilityVSPower

Solution Approach 1:

The patent applies local quality by concentrating all catalytic functionality within the specific Box A region (amino acids 2-22). This localized functional region contains the essential residues for hydrolysis activity, and by focusing the catalytic power in this specific local segment rather than distributing it throughout the entire protein, the invention achieves both high stability and maintained catalytic efficiency.

Inventive Principle:
Principle #3Local quality

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 catalytic peptide effectively catalyzes hydrolysis reactions with enhanced stability compared to enzyme proteins, making it suitable for diverse applications and potentially useful in degrading aggregated proteins associated with diseases like Alzheimer's and ALS.

Implementation Method 1

a catalytic peptide to catalyze a hydrolysis reaction

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

use of a catalytic peptide to catalyze a hydrolysis reaction

Methodology Applied
Scientific EffectCatalysis: Catalysis

Data Source

PatentEP3401326B1Novel peptide exhibiting hydrolytic activity and use thereof
Publication Date: 2022.07.13 OKINAWA INST OF SCI & TECH SCHOOL
  • EP3401326B1 patent drawingFigure 1~2
  • EP3401326B1 patent drawingFigure 3~4
  • EP3401326B1 patent drawingFigure 5~6

AI summary

The present invention provides a novel molecule that catalyzes a hydrolysis reaction and is different from enzyme proteins. The catalytic peptide according to the present invention is a catalytic peptide that catalyzes a hydrolysis reaction, including at least one peptide selected from the group consisting of the following peptides (A1) to (A4): (A1) a peptide consisting of Box A and at least one of an upstream region and a downstream region therefrom in a Tob/BTG protein; (A2) a peptide consisting of a partial region of the peptide (A1); (A3) a peptide that consists of an amino acid sequence obtained by deletion, substitution, addition, and/or insertion of one or more amino acids in an amino acid sequence of the peptide (A1) or (A2) and has hydrolysis activity; and (A4) a peptide consisting of an amino acid sequence with a sequence identity of at least 85% to the amino acid sequence of the peptide (A1) or (A2) and having hydrolysis activity.