Charge-Complementary Peptides for Uricase Delivery
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Solution Overview
Problem
Current self-assembling peptides face challenges in maintaining protein folding and function under neutral, near-physiological conditions, and existing supramolecular biomaterials lack efficient methods for integrating functional molecules like uricase for treating conditions related to monosodium urate crystals, such as gout.
Innovation Solution
Charge-complementary peptides are engineered to self-assemble only under specific conditions, allowing for the integration of uricase proteins into nanofibers and hydrogels, providing a stable and functional platform for treating conditions like gout by modulating uric acid levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If self-assembling peptides are used to deliver therapeutic cargo, then the ability to perform complex tasks and multi-scale hierarchical organization is improved, but the maintenance of protein folding and function under neutral conditions deteriorates
Solution Approach 1:
The invention divides the peptide system into two separate charge-complementary peptides that self-assemble only when mixed, rather than using a single peptide that must maintain structure independently. This segmentation allows each peptide to be stable in isolation while achieving complex assembly functionality when combined.
Solution Approach 2:
The peptides are designed to be pre-stabilized in their individual folded states under neutral conditions before mixing. The self-assembly action is postponed until the peptides are combined, at which point the complementary charges drive assembly while the pre-formed structures maintain their functional integrity.
2Adaptability or versatility
If charge-complementary peptides are engineered to self-assemble under specific conditions, then the integration of functional molecules like uricase is improved, but the complexity of the assembly system increases
Solution Approach 1:
The charge-complementary peptide system serves multiple functions: it provides structural assembly into nanofibers, creates hydrogel networks, and enables integration of various therapeutic cargos including uricase. This universal platform reduces the need for separate systems for each function.
Solution Approach 2:
The charge-complementary interaction between peptides acts as an intermediary mechanism that mediates both the self-assembly process and the integration of functional molecules. The electrostatic attraction serves as a universal binding interface that simplifies the overall system design.
3Reliability
If peptides self-assemble under neutral, near-physiological conditions, then the stability and function of integrated proteins is improved, but the control over assembly timing and location becomes more difficult
Solution Approach 1:
The peptides are prepared and stabilized in their individual folded states under neutral conditions before mixing. The self-assembly action is postponed until the peptides are combined, at which point the complementary charges drive assembly while the pre-formed structures maintain their functional integrity.
Solution Approach 2:
The charge-complementary peptides self-regulate their assembly through electrostatic attraction when mixed under neutral conditions. The system automatically assembles without requiring external guidance, maintaining protein stability while achieving controlled assembly through the inherent chemical properties of the peptides.
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 approach enables the formation of stable nanofibers and hydrogels that effectively deliver uricase, reducing uric acid levels and alleviating symptoms of gout by self-assembling under neutral conditions, maintaining protein function and stability.
Implementation Method 1
charge complementary self-assembling peptides... that can be associated with (e.g., fused to) a therapeutic cargo... and that can contain a positive peptide... and a negative peptide that can include at least 3 amino acids... wherein the positive and the negative peptide can be configured to self-assemble when mixed under a stimulating condition
Implementation Method 2
maintaining protein folding and function under neutral, near-physiological conditions
Implementation Method 3
a uricase protein is fused to a self-assembling peptide... providing a stable and functional platform for treating conditions like gout by modulating uric acid levels
Data Source
AI summary
Provided herein are charge complementary peptides coupled to a cargo polypeptide (e.g., a uricase protein) (e.g., uricase) 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 (e.g., to treat gout).