Multivalent Dendrons for Peptide Immobilization on Metal Oxides

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Solution Overview

Problem

Current methods for immobilizing bioactive peptides on metal oxide surfaces, such as titanium and zirconia, are inefficient and often require complex procedures, leading to low drug efficiency and adverse reactions, while existing surface decoration techniques lack diversity in presenting functional groups for chemical reactions, limiting the effective immobilization and retention of bioactive molecules.

Innovation Solution

Development of multivalent dendrons with a bioactive peptide domain and surface-binding catechol domains, which provide a strong and efficient method for attaching bioactive peptides to metal oxide surfaces like TiO2, ZrO2, and CeO2, utilizing catechol groups for strong adhesion and flexible linkages for enhanced binding affinity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If physical adsorption or encapsulation methods are used to immobilize bioactive peptides on metal oxide surfaces, then the procedure is simple, but the retention and stability of peptides are poor

Engineering Contradiction:
Improvesimplicity of procedureVSAvoidretention and stability of peptides
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The invention uses a composite molecule comprising a dendron with multiple functional groups (catechol groups for metal oxide binding, PEG chains for steric stabilization, and terminal carboxyl groups for peptide conjugation) to achieve both strong peptide retention and procedural simplicity. This single composite molecule replaces complex multi-step chemical conjugation procedures while maintaining high peptide stability on the metal oxide surface.

Inventive Principle:
Principle #40Composite materials

2Reliability

If chemical conjugation methods are used to immobilize bioactive peptides on metal oxide surfaces, then the retention and stability of peptides are improved, but the procedures become complicated and surface properties change during fabrication

Engineering Contradiction:
Improveretention and stability of peptidesVSAvoidcomplexity of procedures
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The dendron molecule is pre-functionalized with multiple catechol groups that are ready to bind to metal oxide surfaces, and pre-equipped with terminal carboxyl groups for peptide conjugation. This preliminary preparation eliminates the need for complex in-situ surface activation steps (such as electrochemical anodization, acid-etching, or oxidation) during the actual immobilization process, thereby reducing procedural complexity while maintaining high peptide retention and stability.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If conventional surface decoration techniques are used, then the surface can be derivatized with bioactive peptides, but the diversity of functional groups for chemical reactions is limited

Engineering Contradiction:
Improvediversity of functional groupsVSAvoideffective immobilization and retention of bioactive molecules
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The dendron molecule is designed as a universal platform with multiple functional groups serving different purposes: catechol groups for binding to various metal oxide surfaces (TiO2, ZrO2, CeO2, Fe3O4), PEG chains for providing steric stabilization and controlling hydrophilicity, and terminal carboxyl groups for conjugating diverse bioactive molecules including peptides, proteins, and small molecules. This multi-functional design enables effective immobilization across different metal oxide surfaces while maintaining versatility in the types of bioactive molecules that can be attached.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 multivalent dendrons achieve strong and stable attachment of bioactive peptides to metal oxide surfaces, enhancing cell attachment, proliferation, and differentiation, with prolonged retention times and improved bioactivity, even at low concentrations, thus addressing the limitations of existing methods.

Implementation Method 1

Catechol group is the functional group of DOPA, which is known to interact with titanium oxide surface through coordination bond or H-bond with pH sensitivity

Methodology Applied
Scientific EffectCoordination bond: Chemical Bonding

Implementation Method 2

Catechol group is the functional group of DOPA, which is known to interact with titanium oxide surface through coordination bond or H-bond with pH sensitivity

Methodology Applied
Scientific EffectHydrogen bond: Chemical Bonding

Implementation Method 3

The presence of 3,4-dihydroxyphenylalanine (DOPA), which is found abundantly in mussel adhesive proteins, has been connected to the strong adhesion of mussels onto multiple surfaces in wet conditions

Methodology Applied
Scientific EffectMultivalent binding:

Data Source

PatentUS10765748B2Composition and methods for tethering bioactive peptides to metal oxide surfaces
Publication Date: 2020.09.08 THE UNIVERSITY OF AKRON
  • US10765748B2 patent drawing
  • US10765748B2 patent drawing
  • US10765748B2 patent drawing

AI summary

In various aspects, embodiments of the present invention are directed to a series of multivalent dendrons containing a bioactive peptide domain and surface-binding catechol domains. In some embodiments, these multivalent dendrons were obtained through solid phase synthesis and have a strong binding affinity to metal oxide surfaces such as, TiO2, ZrO2, CeO2, and Fe3O4, SiO2, as well as other inorganic surfaces such as hydroxyapatite, silver, fluorapatite, calcium carbonate and gold. These catechol-bearing dendrons provide a fast and efficient method to functionalize a wide range of inorganic materials with bioactive peptides and have the potential to be used in coating orthopaedic implants and fixation devices.