Hero Protein Screening for Stress-Stable Active Protein Formulation

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Solution Overview

Problem

Existing methods fail to effectively stabilize proteins against denaturation and aggregation due to various stress conditions, particularly for physiologically active proteins, which can lead to loss of function and disease progression.

Innovation Solution

A screening method is developed to identify proteins with intrinsically disordered structures, known as Hero proteins, which protect and stabilize client proteins by evaluating their stability and aggregation resistance under stress conditions, using tools like IUPred for prediction and heat solubility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional protein stabilization methods are used, then protein structure is maintained under normal conditions, but proteins undergo denaturation and aggregation under stress conditions such as heat, dehydration, and freezing

Engineering Contradiction:

Improveprotein stabilityVSAvoiddenaturation and aggregation under stress

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces intrinsically disordered proteins (IDPs) as intermediary molecules that mediate protection between stress conditions and client proteins. These IDPs act as molecular shields that interact with client proteins and prevent direct damage from stress factors like heat, dehydration, and freezing, thereby resolving the contradiction between maintaining protein stability and preventing stress-induced denaturation

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent exploits the unique physical-chemical parameters of intrinsically disordered proteins, particularly their high hydrophilicity and flexibility, to provide protection. By changing from structured proteins to disordered proteins with specific amino acid compositions (enriched in polar residues), the system achieves enhanced stability under extreme conditions while preventing aggregation

Inventive Principle:

Principle #35Parameter changes

2Reliability

If proteins are highly structured to maintain function, then biological activity is preserved, but susceptibility to denaturation increases under extreme environments

Engineering Contradiction:

Improvebiological activityVSAvoidresistance to denaturation

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

Intrinsically disordered proteins serve as intermediary protective agents that do not replace client proteins but work in conjunction with them. These IDPs form protective complexes with structured client proteins, allowing the client proteins to maintain their native structure and biological activity while gaining enhanced resistance to denaturation under extreme environmental conditions

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs intrinsically disordered proteins as pre-formed protective cushions that are present before stress conditions occur. These IDPs are constitutively expressed or induced in advance to create a protective environment around client proteins, cushioning them against upcoming stressors such as heat shock, dehydration, or freezing events

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

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

Hero proteins maintain protein activity and prevent aggregation even under stress, offering potential therapeutic benefits for diseases caused by abnormal protein aggregation.

Implementation Method 1

proteins having an intrinsically disordered structure are present abundantly in boiled supernatants of cell lysates

Methodology Applied

Scientific EffectIntrinsically disordered structure:

Implementation Method 2

the amino acid compositions of these proteins have tendencies different from those of conventionally-known typical intrinsically disordered regions

Methodology Applied

Scientific EffectHeat solubility:

Data Source

PatentUS12535488B2Screening method for client protein-protecting protein, and physiologically active protein-stabilizing protein and pharmaceutical composition comprising said protein

Publication Date: 2026.01.27 THE UNIV OF TOKYO

AI summary

Provided herein is a novel screening method for a client protein-protecting protein, and a physiologically active protein-stabilizing protein and a pharmaceutical composition using the protein. Also provided herein is a method for screening for a client protein-protecting protein, including the step of evaluating stability of a client protein in the presence of a protein having an intrinsically disordered structure. Also provided herein is an agent for stabilizing a physiologically active protein comprising, as an active ingredient, a protein having any one of amino acid sequences of SEQ ID NOs: 1 to 6; and a pharmaceutical composition including the protein and a physiologically active protein.