Charge-Complementary Peptides for Stable Protein Integration
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Solution Overview
Problem
Current supramolecular biomaterials face challenges in incorporating functional molecules like folded proteins due to aggregation and misfolding during recombinant DNA expression, limiting their functional capabilities and stability in biological environments.
Innovation Solution
Development of charge-complementary peptides that self-assemble only under neutral, near-physiological conditions, allowing for the integration of folded proteins into β-sheet nanofibers, such as CATCH(+ )and CATCH(−) peptides, which combine with cargo polypeptides to form stable nanofibers and hydrogels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If folded proteins are incorporated into supramolecular biomaterials during recombinant DNA expression, then functional capabilities are enhanced, but aggregation and misfolding occur during expression
Solution Approach 1:
The patent divides the protein structure into two functional segments: a folded protein segment that performs the biological function and a peptide segment that mediates self-assembly. This segmentation allows the folded protein to be incorporated into supramolecular biomaterials without causing aggregation or misfolding during recombinant DNA expression, as the peptide segment handles the assembly process separately.
Solution Approach 2:
The patent introduces a peptide segment as an intermediary between the folded protein and the supramolecular structure. This peptide segment acts as a mediator that facilitates the integration of folded proteins into β-sheet nanofibers and hydrogels, enabling stable incorporation while preventing direct aggregation of the folded protein during expression.
2Reliability
If peptides are designed to self-assemble under neutral conditions, then protein folding is maintained, but self-assembly is delayed until appropriate conditions are met
Solution Approach 1:
The patent employs pH-responsive peptide segments that undergo conformational changes based on pH conditions. Under neutral or near-physiological pH, the peptide segments remain in a state that maintains protein folding stability. When the pH is adjusted or other stimuli are applied, the peptide segments undergo parameter changes that trigger self-assembly into nanofibers and hydrogels, thus controlling the timing of assembly while maintaining folding integrity.
3Stability of the object's composition
If charge-complementary peptides are used for co-assembly, then stable nanofibers are formed, but complex sequence design is required
Solution Approach 1:
The patent applies local quality by designing specific charge-complementary regions within the peptide sequences. Instead of requiring complex sequences throughout the entire peptide, the invention incorporates localized charged amino acid motifs (such as alternating positive and negative charges) that provide the necessary electrostatic interactions for stable nanofiber formation. This localized approach simplifies the overall sequence design while maintaining stability.
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
Enables the creation of stable, functional supramolecular biomaterials with integrated folded proteins, maintaining protein folding and function while preventing premature self-assembly, thus enhancing their applicability in biomedical and biotechnological applications.
Implementation Method 1
charge-complementary peptides that self-assemble only under neutral, near-physiological conditions
Implementation Method 2
self-assembling peptides that can contain a positive peptide... and a negative peptide... configured to self-assemble when mixed
Data Source
AI summary
Provided herein are charge complementary peptides that can be optionally coupled to a cargo polypeptide that are capable of self-assembling under stimulating conditions. The charge complementary peptides can be capable of forming supramolecular structures. Also provided herein are methods of using the charge complementary peptides provided herein.