Dimeric Collagen Hybridizing Peptides for In Vivo Detection

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Solution Overview

Problem

Current methods for detecting and targeting degraded collagen are inadequate, as they often require denaturation of collagen triple helices, which can be damaging and inefficient, especially for in vivo applications.

Innovation Solution

Development of peptide conjugates comprising a dimeric collagen hybridizing peptide with a specific sequence (GXY)n, where G is glycine, X and Y are any amino acids, and n is between 3 and 12, linked by a spacer moiety and a branch point, allowing for binding to denatured collagen without prior denaturation, enhancing folding kinetics and binding affinity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used to detect and target degraded collagen, then detection and targeting can be achieved, but collagen triple helices must be denatured first which is damaging and inefficient

Engineering Contradiction:

Improvedetection and targeting capabilityVSAvoidcollagen denaturation damage

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The peptide is designed to perform the binding action before denaturation is required. The dimeric collagen hybridizing peptide binds to native collagen triple helices in their folded state, eliminating the need for prior denaturation step and avoiding the harmful effects of thermal or chemical denaturation while maintaining detection and targeting capability

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention changes the binding parameter from requiring denatured collagen to binding native folded collagen. By modifying the peptide structure to a dimeric form with specific hybridizing sequences, the peptide can recognize and bind to the native triple helical structure, fundamentally changing the condition under which collagen binding occurs and eliminating the need for damaging denaturation

Inventive Principle:

Principle #35Parameter changes

2Device complexity

If monomeric collagen hybridizing peptides are used, then simplicity is maintained, but refolding rates are slow and binding affinity is limited

Engineering Contradiction:

Improvepeptide structure simplicityVSAvoidrefolding rate and binding affinity

Core Design Contradiction:

Device complexityVSProductivity

Solution Approach 1:

Two monomeric collagen hybridizing peptides are merged into a single dimeric structure through a linker. This combination allows the peptide to bind two collagen molecules simultaneously or bind with higher affinity to a single collagen molecule, thereby increasing binding affinity and refolding rate while maintaining relative structural simplicity through the use of a straightforward dimeric architecture

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The dimeric peptide is constructed as a composite structure combining two peptide units with a linker and branch point. This composite design leverages the collective binding capability of both monomeric units while introducing cooperative effects that enhance overall binding affinity and refolding kinetics compared to a single monomeric peptide

Inventive Principle:

Principle #40Composite materials

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 conjugates can bind to denatured collagen effectively at physiological temperatures without preheating, demonstrating faster refolding rates and higher affinity compared to monomeric counterparts, making them suitable for in vivo applications in detecting and treating collagen-related diseases.

Implementation Method 1

a dimeric collagen hybridizing peptide comprising a first and second collagen hybridizing peptide

Methodology Applied

Scientific EffectHybridization:

Implementation Method 2

demonstrating faster refolding rates and higher affinity compared to monomeric counterparts

Methodology Applied

Scientific EffectRefolding: Folding

Data Source

PatentUS11684675B2Dimeric collagen hybridizing peptides and methods of using

Publication Date: 2023.06.27 UNIV OF UTAH RES FOUND

AI summary

Disclosed are peptide conjugates comprising an active agent, a spacer moiety, and a dimeric collagen hybridizing peptide comprising a first and second collagen hybridizing peptide, a linker; and a branch point, wherein the first and second collagen hybridizing peptides comprise the sequence of at least (GXY)n, wherein G is glycine, wherein X and Y are any amino acid, and wherein n is any number between 3 and 12. Also disclosed are methods of detecting denatured collagen in a sample comprising contacting a composition comprising any one of the disclosed peptide conjugates to a sample, wherein the active agent comprises a therapeutic agent, and detecting the presence or absence of binding of the peptide conjugate to denatured collagen, the presence of binding indicating the presence of denatured collagen in the sample. Also disclosed are methods of treating a disease or injury involving collagen damage comprising administering to a subject having a disease or injury involving collagen damage any one of the disclosed peptide conjugates.