Interferor Peptides for Controlled Protein Aggregation
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Solution Overview
Problem
Current methods for inducing protein aggregation often require a solubilizing moiety and are complex to synthesize, and there is a need for molecules that can remain soluble while specifically inducing aggregation of target proteins for therapeutic and diagnostic applications.
Innovation Solution
Development of interferor molecules with a specific structure, comprising aggregation-inducing sequences flanked by aggregation-breaking residues, which do not require a solubilizing moiety and can efficiently induce stable intermolecular beta-aggregate formation with target proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If aggregation-inducing sequences are used to induce protein aggregation, then the ability to induce aggregation is improved, but the solubility of the molecule deteriorates
Solution Approach 1:
The molecule is divided into distinct functional segments: aggregation-inducing sequences (Y) flanked by aggregation-breaking residues (X). This segmentation allows the aggregation-inducing core to function effectively while the breaking residues prevent premature aggregation and maintain solubility. The molecule structure (X2i-1-Yi-X2i-Zi)n clearly separates these functions into discrete units.
Solution Approach 2:
Different regions of the molecule have different local properties: the Y regions are designed with high aggregation propensity (hydrophobic amino acids with specific patterns) to induce aggregation, while the X regions have low aggregation propensity (aggregation-breaking residues) to maintain solubility and prevent premature aggregation. This local differentiation of properties resolves the contradiction between aggregation ability and solubility.
2Stability of the object's composition
If solubilizing moiety is added to maintain solubility, then the solubility is improved, but the device complexity increases
Solution Approach 1:
The aggregation-breaking residues (X) serve multiple functions: they maintain solubility of the molecule, prevent premature aggregation, and flank the aggregation-inducing sequences to control their activity. This multi-functionality eliminates the need for separate solubilizing moieties, reducing molecular complexity while achieving both solubility and aggregation induction capabilities.
3Reliability
If aggregation-inducing sequences are made more potent, then the aggregation induction ability is improved, but the premature aggregation increases
Solution Approach 1:
Aggregation-breaking residues (X) are placed flanking the aggregation-inducing sequences (Y) to preemptively prevent premature aggregation. These breaking residues create a protective effect that counteracts the aggregation tendency of the Y sequences before they can aggregate prematurely, while still allowing controlled aggregation of target proteins when needed.
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
These molecules effectively inhibit the function of biologically active proteins by inducing aggregation, offering therapeutic and diagnostic applications, as well as uses in agbio, white biotech, and research, with improved solubility and synthesis ease.
Implementation Method 1
Protein aggregation is caused by the misfolding and subsequent agglutination of proteins in insoluble agglomerates. Protein aggregation is essentially a self-association process in which many identical protein molecules form higher order conglomerates of low solubility that eventually precipitate.
Implementation Method 2
The most common mechanism by which misfolded proteins aggregate consists in the self-association of specific polypeptide segments from identical proteins into a growing intermolecular beta sheet. These aggregation-nucleating segments are generally short, consisting of 5-15 residues, and can be accurately predicted using available biophysical algorithms.
Data Source
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Figure 4B~5A
AI summary
The present application belongs to the field of functional peptides and more particularly to the field of controlled protein aggregation. The invention discloses molecules of a peptide structure as defined in the claims and methods of using such molecules for therapeutic applications and for diagnostic uses, as well as in other applications such as in the agbio field and in industrial biotechnology. The molecules can be used for curing and/or stabilizing infections such as bacterial,fungal and viral diseases, but are also useful in non-infectious human and veterinary diseases. The molecules can also be used for the detection of protein biomarkers and for the prognosis and diagnosis of a variety of diseases.