Activatable Peptide Probes for Clot Imaging
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Solution Overview
Problem
Current diagnostic tools for conditions associated with proteolytic activity, such as coronary heart disease and cancer, are often invasive, costly, and lack sensitivity, making it difficult to detect proteolytic events effectively.
Innovation Solution
Development of activatable and detectable membrane-interacting peptides that interact with phospholipid bilayers, specifically designed to accumulate at sites of proteolytic activity, allowing for direct imaging of active clotting or other proteolytic processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional imaging approaches are used to assess cardiac damage, then visualization can be achieved, but the cost is high, sensitivity is low, and radiation or imaging agent toxicity occurs
Solution Approach 1:
The patent uses a peptide probe as an intermediary molecule that specifically binds to phospholipid bilayers at sites of proteolytic activity. This peptide mediator enables indirect detection of clotting events through optical imaging, avoiding direct radiation exposure while maintaining detection sensitivity through targeted accumulation at disease sites
Solution Approach 2:
The patent replaces radiation-based imaging mechanisms with optical detection methods using fluorescently labeled peptides. This substitution eliminates radiation toxicity while achieving comparable or superior sensitivity through the high specificity of peptide-phospholipid bilayer interactions at proteolytic sites
2Measurement precision
If biomarker assays are used for indirect assessment of cardiac damage, then diagnosis can be obtained, but multiple samples are required over time which is time-consuming
Solution Approach 1:
The patent employs a peptide probe that has been pre-designed and synthesized with fluorescent labeling before administration. This preliminary preparation allows the probe to be ready for immediate detection upon injection, enabling single-time-point imaging rather than requiring multiple sequential samples over time
Solution Approach 2:
The patent creates a visual copy or image of the proteolytic activity site through fluorescent imaging, replacing the need for multiple physical blood samples. The optical signal provides a direct visual representation of clot location and extent, eliminating repeated sampling while maintaining diagnostic accuracy
3Measurement precision
If direct procedures are used to identify cardiac damage location and extent, then accurate information is obtained, but the procedures are invasive and not appropriate for all patients
Solution Approach 1:
The peptide probe performs self-targeting to sites of proteolytic activity through its inherent affinity for phospholipid bilayers. Once administered, the probe autonomously accumulates at clot locations without requiring invasive guidance procedures, providing accurate location detection through a simple non-invasive injection and imaging protocol
Solution Approach 2:
The patent uses fluorescent labeling that produces visible color changes or optical signals at sites of proteolytic activity. This optical visualization method replaces invasive procedural interventions with a non-invasive imaging approach that provides equal or superior location accuracy through fluorescent signal detection
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 non-invasive, sensitive detection of proteolytic events by accumulating at sites of activity, facilitating early diagnosis and monitoring of conditions like coronary heart disease and cancer.
Implementation Method 1
X2 is a cleavable linker that can be cleaved to release cleavage products from the compound
Implementation Method 2
A is a membrane-interacting peptide region having a plurality of nonpolar hydrophobic amino acid residues that, following separation from portion Z, is capable of interacting with a phospholipid bilayer
Data Source
AI summary
The present disclosure provides activatable and detectable membrane-interacting peptides that, following activation, can interact with phospholipid bilayers, such as cell membranes. The present disclosure also provides methods of use of such compounds. The compounds of the present disclosure are of the general structure X1a-A-X2-Z-X1b, where A is a membrane-interacting peptide region having a plurality of nonpolar hydrophobic amino acid residues that, following separation from portions Z, is capable of interaction with a phospholipid bilayer; Z is an inhibitory peptide region that can inhibit the activity of portion A; X2 is a cleavable linker that can be cleaved to release cleavage products from the compound; and X1a and X1b are optionally-present chemical handles that facilitate conjugation of various cargo moieties to the compound. Prior to cleavage of the composition at X2, the composition acts as a promolecule that does not associate with cellular membranes to a significant or detectable level. Following cleavage at cleavable linker X2, the cleavage product including portion A is free to interact with a phospholipid bilayer (e.g., a cell membrane), and thus accumulate at a site associated with a cleavage-promoting environment. Detection of the membrane-associated cleavage product can be accomplished by detection of a moiety attached through X1a and/or X1b. Such compositions can be used in a variety of methods, including, for example, use in directly imaging active clotting within a subject.