FGF7 Polypeptide Salt-Bridge Design for Thermal Stability

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Solution Overview

Problem

FGF7 polypeptides exhibit low thermal stability at room temperature, leading to rapid activity loss in aqueous solutions, limiting their use in industrial applications.

Innovation Solution

A thermally stable FGF7 polypeptide is developed through site-specific mutagenesis, specifically altering amino acids at positions 120, 126, and 178 to form salt bridges and disulfide bonds, enhancing temperature stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If FGF7 polypeptide is used in aqueous solution at room temperature or higher, then cell regeneration and proliferation functions are maintained, but thermal stability is poor leading to rapid activity loss within 24 hours

Engineering Contradiction:

Improveactivity stabilityVSAvoidthermal stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by introducing specific amino acid mutations (K126E, K178E, A120C) that alter the molecular parameters of FGF7, creating new salt bridges and disulfide bonds that fundamentally change the protein's thermal stability properties while preserving its biological activity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite structural framework within the protein by combining multiple stabilizing elements (salt bridges between R122-E73 and R122-E126, disulfide bonds between C80-C84 and C133-C137) to achieve synergistic thermal stabilization

Inventive Principle:

Principle #40Composite materials

2Duration of action of stationary object

If FGF7 polypeptide is stored in aqueous solution, then biological activity is maintained initially, but activity is lost rapidly after 24 hours due to thermal instability

Engineering Contradiction:

Improvestorage durationVSAvoidactivity retention

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent performs preliminary stabilization by pre-introducing stabilizing mutations and forming disulfide bonds before storage, which prevents activity loss during the subsequent 24-hour storage period in aqueous solution

Inventive Principle:

Principle #10Preliminary action

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 modified FGF7 polypeptide maintains activity during distribution and storage, offering improved thermal stability compared to wild-type FGF7.

Implementation Method 1

Each of a 73rd glutamic acid (E) and a 125th glutamic acid (E) form a salt bridge with a 122nd arginine (R)

Methodology Applied

Scientific EffectSalt bridge: Chemical Bonding

Implementation Method 2

a 80th cysteine (C) and 84th cysteine (C) are disulfide bonded

Methodology Applied

Scientific EffectDisulfide bond: Chemical Bonding

Data Source

PatentUS12479897B2Thermally stable FGF7 polypeptide and use of the same

Publication Date: 2025.11.25 KOREA INSTITUTE OF OCEAN SCIENCE & TECHNOLOGY

AI summary

A thermally stable polypeptide having FGF7 activity is provided. The polypeptide is a thermally stable polypeptide having FGF7 activity, wherein, in SEQ ID NO: 1, a 120th alanine (A) is substituted with cysteine (C), one including at least one substitution selected from substitution of a 126th lysine (K) with aspartic acid (D) and a 178th lysine (K) with glutamic acid (E) or aspartic acid (D) forms a salt bridge with a 175th arginine (R), and a 133rd cysteine (C) and a 137th cysteine (C) are disulfide bonded.