Alkali-Stable IgG-Binding Peptide via Disulfide Cross-Linking

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Solution Overview

Problem

Protein A columns used for IgG purification are contaminated with protein A, which is immunogenic and costly to purify, and existing peptide ligands have affinity issues with alkaline solutions.

Innovation Solution

A solid-phase support with an IgG-binding peptide, specifically the amino acid sequence GPDCAYHRGELVWCTFH, where sulfide groups in cysteine residues are cross-linked using a specific linker, enhancing stability and resistance to alkaline conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If protein A is used as an affinity ligand for IgG purification, then IgG binding capacity is improved, but contamination with immunogenic protein A and endotoxin occurs, increasing cost and safety concerns

Engineering Contradiction:
ImproveIgG binding capacityVSAvoidprotein A contamination and endotoxin
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The invention extracts only the essential IgG-binding functional domain from the full protein A molecule, using a specifically designed peptide sequence (GPDCAYHRGELVWCTFH) that captures IgG without requiring the complete protein A structure. This extraction eliminates the immunogenic and endotoxin-containing portions of protein A while retaining the affinity binding function.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates a simplified peptide copy of the IgG-binding function found in protein A. Instead of using the complex, multi-domain protein A structure, a compact peptide sequence is designed and synthesized that replicates the essential binding interface, providing the same functional outcome with reduced complexity and eliminated harmful components.

Inventive Principle:
Principle #26Copying

2Reliability

If a peptide ligand with disulfide bond cross-linking is used for IgG purification, then initial IgG binding capacity is achieved, but affinity decreases after repeated washing with alkaline solution

Engineering Contradiction:
ImproveIgG binding capacityVSAvoidpeptide stability under alkaline conditions
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention changes the chemical parameter of the cross-linking bond from a disulfide bond (S-S) to a carbon-based cross-linkage. This parameter change transforms the bond's chemical stability characteristics, making it resistant to alkaline hydrolysis while maintaining the structural integrity needed for IgG binding. The cross-linked peptide structure remains stable during repeated alkaline washing cycles.

Inventive Principle:
Principle #35Parameter changes

3Object-generated harmful factors

If protein A is highly purified to prevent contamination, then safety and cost issues are improved, but the purification process becomes more complex and expensive

Engineering Contradiction:
Improveprotein A and endotoxin contaminationVSAvoidpurification process complexity
Core Design Contradiction:
Object-generated harmful factorsVSDevice complexity

Solution Approach 1:

The invention extracts only the essential IgG-binding functional domain from the full protein A molecule, using a specifically designed peptide sequence (GPDCAYHRGELVWCTFH) that captures IgG without requiring the complete protein A structure. This extraction eliminates the immunogenic and endotoxin-containing portions of protein A while retaining the affinity binding function.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates a simplified peptide copy of the IgG-binding function found in protein A. Instead of using the complex, multi-domain protein A structure, a compact peptide sequence is designed and synthesized that replicates the essential binding interface, providing the same functional outcome with reduced complexity and eliminated harmful components.

Inventive Principle:
Principle #26Copying

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 maintains high IgG binding capacity even after alkaline washing, enabling efficient and cost-effective IgG purification without protein A contamination.

Implementation Method 1

cross-linking sulfide groups in cysteine residues in a peptide by a linker having a specific structure

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Implementation Method 2

the peptide being capable of binding to human IgG

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentEP3543251B1Solid support containing igg-binding peptide, and method for separating igg
Publication Date: 2023.08.30 DAICEL CORP
  • EP3543251B1 patent drawingFigure 1
  • EP3543251B1 patent drawingFigure 2
  • EP3543251B1 patent drawingFigure 3

AI summary

The present invention provides an IgG-binding peptide which can be used for the purification of IgG and has excellent stability, e.g., alkali stability. The present invention also provides a method for purifying IgG using the IgG-binding peptide. Specifically, the present invention relates to a solid-phase support including an IgG-binding peptide, an IgG separation column including the solid-phase support, a kit including the solid-phase support or the column, and a method for purifying IgG using the solid-phase support or the column.