Self-assembling Peptides with Hyaluronic Acid Binding Domains
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Solution Overview
Problem
Existing self-assembling peptides used in medical applications have limited efficacy and viability in vivo, necessitating the development of novel peptides that can effectively bind to extracellular matrix components like hyaluronic acid.
Innovation Solution
Design and development of self-assembling peptides comprising BX7B domains, where B is a basic amino acid and X is any amino acid except an acidic amino acid, which exhibit robust binding to hyaluronic acid and form nanofibers, enhancing their therapeutic potential.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing self-assembling peptides are used in medical applications, then they can be administered to treat conditions, but their efficacy and viability in vivo are limited
Solution Approach 1:
The patent introduces specific BX7B domains (basic amino acid-X-amino acid-X-amino acid-basic amino acid pattern) at particular positions within the peptide sequence to create localized hyaluronic acid binding regions. This local modification allows the peptide to maintain its self-assembling properties while gaining enhanced ECM binding capability through the basic amino acids that interact with the negatively charged hyaluronic acid.
Solution Approach 2:
The invention creates composite functional peptides by combining multiple domains with different functions: BX7B domains for hyaluronic acid binding, beta-sheet forming regions for self-assembly, and hydrophobic/hydrophilic segments for nanofiber formation. This composite structure integrates ECM binding capability with self-assembling properties to overcome the limitations of existing peptides.
2Strength
If self-assembling peptides are designed to bind to hyaluronic acid, then binding affinity is enhanced, but the complexity of peptide structure increases
Solution Approach 1:
The peptide is divided into distinct functional segments: BX7B domains for hyaluronic acid binding, beta-sheet forming regions for self-assembly, and hydrophobic/hydrophilic segments for nanofiber formation. This segmentation allows each domain to perform its specific function independently while contributing to the overall enhanced binding affinity and self-assembling capability.
Solution Approach 2:
The patent systematically varies parameters within the BX7B domains, such as the identity of basic amino acids (arginine, lysine, histidine), the spacing between basic amino acids (X represents 0-7 amino acids), and the number of BX7B domains (1-5 domains), to optimize binding affinity while maintaining manageable structural complexity.
3Reliability
If peptides form nanofibers at higher concentrations, then therapeutic efficacy is improved, but the concentration required increases the dose
Solution Approach 1:
The peptides are designed to autonomously self-assemble into nanofibers through their intrinsic beta-sheet forming capability and hydrophobic/hydrophilic segregation, without requiring external assistance or catalysts. This self-service mechanism allows the peptides to form functional nanofibers at lower concentrations compared to systems requiring external assembly conditions.
Solution Approach 2:
The peptide structure incorporates dynamic elements that allow concentration-dependent self-assembly: at lower concentrations, monomers remain soluble; at higher concentrations, they spontaneously assemble into beta-sheet nanofibers. This dynamic behavior enables the system to adapt its structure and function based on the local concentration, improving therapeutic efficacy where needed while minimizing overall dosage.
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 novel peptides demonstrate enhanced binding affinity and self-assembly capabilities, forming beta-sheet structures and nanofibers that outperform existing peptides, particularly at higher concentrations, thereby improving their efficacy in medical applications such as treating inflammatory conditions, cancer, and promoting wound healing.
Implementation Method 1
the self-assembling peptide has a propensity to form β-sheet secondary structure
Implementation Method 2
a self-assembling peptide comprising a plurality of BX7B domains, wherein B is a basic amino acid and X is any amino acid except an acidic amino acid... wherein the self-assembling peptide binds to hyaluronic acid
Implementation Method 3
Self-assembling peptides have been used in various research efforts... provided herein are self-assembling peptides... provided herein is a nanofiber comprising a plurality of self-assembling peptides
Data Source
AI summary
Provided herein are self-assembling peptides comprising hyaluronic acid binding domains, nanofibers and systems comprising the same, and methods of use thereof.