Calcium Binding Peptides for Targeted Tissue Remineralization

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Solution Overview

Problem

Current methods for remineralization of decalcified tissues rely on flooding the area with free or protein-bound calcium, lacking specificity and efficiency in targeting calcium to surfaces for enhanced calcification, and existing diagnostic methods for calcification are invasive, labor-intensive, or expose subjects to radiation.

Innovation Solution

Development of small calcium binding peptides composed of Asp-Ser-Ser motifs that specifically bind to calcium phosphate surfaces, recruiting calcium phosphate and serving as moieties for attaching fluorescent labels, allowing targeted remineralization and diagnosis of demineralized tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If small fluorescent molecules or large calcium-binding proteins are used to bind calcium phosphate surfaces, then calcium binding capability is achieved, but specificity and efficiency in targeting calcium to surfaces for enhanced calcification is insufficient

Engineering Contradiction:
Improvespecificity of calcium bindingVSAvoidefficiency of calcium recruitment
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent segments the calcium-binding function into small peptide molecules (e.g., 5-20 amino acids) containing specific motifs like Asp-Ser-Ser, rather than using large proteins. This segmentation increases efficiency by allowing smaller, more mobile molecules to rapidly recruit calcium phosphate to surfaces while maintaining binding specificity through the conserved amino acid motifs.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent optimizes parameters including peptide length (5-20 residues), amino acid composition (specific Asp-Ser-Ser motifs), and repeat units (n=3-15) to achieve both high specificity and efficiency. By adjusting these parameters, the peptides bind calcium phosphate with high affinity while remaining small enough to efficiently target and recruit calcium to demineralized tissue surfaces.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If conventional remineralization methods flood the area with free or protein-bound calcium, then calcium availability is increased, but targeting specificity to surfaces for enhanced calcification is lacking

Engineering Contradiction:
Improvecalcium availabilityVSAvoidtargeting specificity
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent introduces calcium-binding peptides as intermediary molecules that mediate between available calcium phosphate in the environment and demineralized tissue surfaces. These peptides act as carriers that specifically transport and deposit calcium phosphate at target sites, providing both quantity (calcium availability) and reliability (targeting specificity) simultaneously.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts the essential calcium-binding function from large proteins or free calcium and concentrates it into small, targeted peptide molecules. By taking out only the necessary amino acid motifs (e.g., Asp-Ser-Ser repeats) required for calcium binding, the peptides achieve high targeting specificity while maintaining calcium recruitment capability.

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If existing diagnostic methods for calcification are used, then detection capability is achieved, but the methods are invasive, labor-intensive, or expose subjects to radiation

Engineering Contradiction:
Improvedetection capabilityVSAvoidinvasiveness and radiation exposure
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses fluorescently labeled calcium-binding peptides that emit light when bound to calcium phosphate surfaces, enabling non-invasive optical detection of demineralized tissues. This color/fluorescence change provides high measurement precision for detecting calcification status without invasiveness or radiation exposure, directly addressing the technical contradiction.

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent replaces mechanical/invasive diagnostic methods (biopsies, surgical exposure) with optical detection using fluorescent peptides. By substituting mechanical systems with optical fields, the detection capability is maintained while eliminating harmful factors such as invasiveness and radiation exposure.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 peptides effectively induce calcium phosphate crystal growth on demineralized surfaces, promoting remineralization and enabling specific visualization and targeting of calcified tissues, reducing the need for invasive diagnostics and improving therapeutic delivery to affected areas.

Implementation Method 1

calcium binding peptides comprise the three amino acid repeat sequence (X-Y-Z) n, wherein X is aspartic acid, Y and Z serine, phosphoserine, or phosphothreonine... wherein said calcium binding peptides bind calcium phosphate

Methodology Applied
Scientific EffectElectrostatic interaction: Ion Repulsion/Attraction

Implementation Method 2

the peptides effectively induce calcium phosphate crystal growth on demineralized surfaces, promoting remineralization

Methodology Applied
Scientific EffectNucleation: Nucleation

Data Source

PatentEP1957094B1Calcium binding peptides
Publication Date: 2015.09.16 RGT UNIV OF CALIFORNIA
  • EP1957094B1 patent drawingFigure 1A~1D
  • EP1957094B1 patent drawingFigure 2A~2D
  • EP1957094B1 patent drawingFigure 3A~3D

AI summary

Disclosed herein are a class of compounds comprising peptides of the sequence (X-Y-Z)n, wherein X is an amino acid selected from aspartic acid, glutamic acid, asparagine, alanine and glutamine, and Y and Z are amino acids selected from alanine, serine, threonine, phosphoserine, phosphothreonine, and their derivatives. These compounds have the property of binding tightly and specifically to calcified surfaces, making them useful for a variety of applications including remineralization of tooth and bone surfaces, diagnosis of bone and tooth defects, treatment of bone and tooth defects, and analysis of the presence and location of calcified deposits both in vitro and in vivo and in industrial, synthetic, medical, dental, and research applications where identification, localization, or manipulation of calcification is desirable.