Magnetic Particle-Binding Peptides for Stable Nanoparticle Functionalization

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Solution Overview

Problem

Current methods for functionalizing magnetic nanoparticles for binding biomolecules are inefficient due to the need for application-specific modifications, which can lead to instability and high costs, and existing surface modifications often result in the leakage of toxic ions or loss of enzymatic activity.

Innovation Solution

A peptide sequence of 5 to 30 amino acids, with at least 2/3 being negatively charged, and specific neutral or polar amino acids, designed to bind to magnetic iron oxide surfaces, eliminating the need for application-specific functionalization and enabling reversible or irreversible binding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If metal ion chelating molecules like nitrilotriacetic acid are attached to MNP surface to bind His-tagged biomolecules, then binding capability is achieved, but toxic metal ions leak and surface functionalization becomes unstable

Engineering Contradiction:
Improvesurface functionalization stabilityVSAvoidtoxic metal ion leakage
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and eliminates the metal ion chelating molecules from the functionalization system, replacing them with a peptide sequence that binds directly to the MNP surface without requiring metal ions. This removes the source of toxic metal ion leakage while maintaining binding capability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The peptide sequence serves as a stable, non-toxic alternative to metal ion chelators. Once attached to the MNP surface, it provides durable functionalization without the instability and toxicity issues of metal-based systems.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If glutathione, streptavidin, biotin or protein A are used for protein adsorption on magnetic particles, then binding capability is improved, but costs increase to over 400 to several thousand euros per gram

Engineering Contradiction:
Improvebinding capabilityVSAvoidcost per gram
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The peptide sequence is significantly cheaper than glutathione, streptavidin, biotin or protein A. It provides cost-effective functionalization while maintaining binding capability, reducing costs from thousands of euros per gram to a fraction of that amount.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent changes the chemical composition parameter of the functionalization layer from expensive proteins and peptides to a synthetic peptide sequence with specific amino acid composition (rich in negatively charged residues like glutamic acid and aspartic acid), achieving both cost reduction and functional performance.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If covalent immobilization techniques such as amino-silanization are used, then binding stability is improved, but complexity increases and enzymatic activity is lost due to reaction of catalytic amino acids

Engineering Contradiction:
Improvebinding stabilityVSAvoidimmobilization complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent extracts and removes the complex covalent immobilization chemistry (amino-silanization) from the process, replacing it with a simpler peptide sequence that provides stable binding through its amino acid composition without requiring complex chemical reactions.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The peptide sequence provides stable functionalization without the complexity of covalent immobilization techniques. It maintains enzymatic activity by avoiding reactions with catalytic amino acids while still achieving durable binding to the MNP surface.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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

This peptide sequence allows for efficient and cost-effective binding of biomolecules to magnetic nanoparticles, reducing the need for costly surface modifications and enabling convenient recycling of magnetic particles, while maintaining enzymatic activity and stability.

Implementation Method 1

at least 2/3 of said amino acids have a functional group or side chain which is negatively charged at neutral pH

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentEP3512869B1Magnetic particle-binding peptides
Publication Date: 2024.02.28 TECHNISCHE UNIVERSITAT MUNCHEN
  • EP3512869B1 patent drawingFigure 1
  • EP3512869B1 patent drawingFigure 2
  • EP3512869B1 patent drawingFigure 3(A)~3(B)

AI summary

The present invention relates to a peptide consisting of a sequence of 5 to 30, preferably 6 to 12, most preferably 10 to 12 amino acids, wherein (a) at least 2/3 of said amino acids have a functional group or side chain which is negatively charged at neutral pH; (b) amino acids which do not have a functional group or side chain which is negatively charged at neutral pH, if present, meet one or both of requirements (i) and (ii): (i) none of them has a functional group or side chain which is positively charged at neutral pH; and (ii) at least one of them has a side chain which does not bear a net charge at neutral pH or which has a functional group or side chain that does not bear a net charge at neutral pH.