Peptide Probe for Pathological Collagen Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for detecting pathological collagen are inefficient due to complex steps, weak affinity, poor specificity, and the inability to distinguish normal collagen from pathological collagen, with peptide probes prone to trimer formation that complicates quantification and increases toxicity risks.
Innovation Solution
A peptide probe with (Gly-Hyp-Pro)n repetitive sequences, modified with a signal molecule at the N-terminal, maintains a stable single-stranded conformation without trimerization, allowing for accurate quantification and specific binding to pathological collagen without pretreatment, using natural amino acids to enhance biocompatibility and reduce toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If peptide probes with (Gly-Pro-Hyp)n repetitive sequences are used to bind to pathological collagen, then specificity for pathological collagen is improved, but the probes spontaneously form trimers and lose their ability to bind to pathological collagen
Solution Approach 1:
The patent changes the chemical structure parameters of the peptide probe by introducing a photocleavable nitrobenzyl group at the N-terminal position. This structural modification prevents trimer formation while maintaining the ability to bind to pathological collagen, resolving the contradiction between specificity and binding ability.
Solution Approach 2:
The photocleavable nitrobenzyl group acts as an intermediary that temporarily occupies the N-terminal position, preventing trimerization. Upon irradiation, this intermediary is cleaved off, releasing the peptide probe in its active single-stranded form for binding to pathological collagen.
2Reliability
If pretreatment methods such as heating are used to transform peptide probes into single-stranded state, then binding ability to pathological collagen is improved, but tissue damage occurs and quantification of probe monomers becomes difficult
Solution Approach 1:
The photocleavable nitrobenzyl group is introduced during the synthesis of the peptide probe, performing the trimer prevention action in advance. This eliminates the need for post-application heating treatment, thereby avoiding tissue damage while maintaining probe monomer quantification accuracy.
3Reliability
If modifications to the (Gly-Pro-Hyp)n sequence are made to drive the peptide probe to form a single-stranded conformation, then binding ability is improved, but the difficulty and cost of peptide probe synthesis greatly increase
Solution Approach 1:
The patent segments the solution into two parts: a commercially available photocleavable nitrobenzyl group and the (Gly-Pro-Hyp)n peptide sequence. This segmentation allows the difficult-to-synthesize single-stranded conformation to be achieved by combining a simple building block with the peptide sequence, rather than modifying every amino acid in the sequence.
4Reliability
If larger groups are modified to the side chains of peptide probes to drive single-stranded conformation, then binding ability is improved, but toxicity risk for in vivo imaging applications significantly increases
Solution Approach 1:
The photocleavable nitrobenzyl group serves as a temporary, disposable modification that is cleaved off after serving its trimer-prevention function. This eliminates the need for permanent toxic modifications, as the nitrobenzyl group is removed along with the peptide probe after use, minimizing long-term toxicity risks.
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 peptide probe demonstrates high selectivity and specificity for pathological collagen, avoiding tissue damage and enabling effective detection and imaging in clinical applications, particularly in arthritis diagnosis and histopathological staining.
Implementation Method 1
peptide probes with (Gly-Pro-Hyp)n repetitive sequences can specifically bind to some of unfolding sites in pathological collagen while remaining single-stranded
Implementation Method 2
the signal molecule X is fluorescein dye, coumarin dye, rhodamine dye, cyanine dye, BODIPY dye, tetraphenylethylene dye, and one or more of hexaphenylmethylsilane dyes, stilbene anthracene dyes, semiconductor quantum dots, carbon quantum dots, perovskite quantum dots, rare earth ion complexes, metal frame materials, up-conversion rare earth nanomaterials and long afterglow nanomaterials
Data Source
AI summary
The invention belongs to the technical field of collagen detection, and in particular relates to a peptide probe for the specific detection of pathological collagen in tissues, the preparation methods and applications. The peptide probe disclosed in this invention comprises a peptide sequence (Gly-Hyp-Pro)n and a signal molecule modified at the N-terminal of the peptide sequence (Gly-Hyp-Pro)n. The peptide sequence (Gly-Hyp-Pro)n can maintain a stable single-stranded conformation without introducing other components, and will not form a trimer state at all. After the N-terminal of the peptide sequence is connected with a signal molecule, it can be used as a peptide probe for the detection of pathological collagen. The preparation method of the peptide probe is simple. Compared with the existing peptide (GPO, GPP or GOO) probe, it can continuously maintain 100% single-stranded structure, and the concentration of the single-chain probe can be accurately quantified. Moreover, this peptide probe can recognize pathological collagen in tissues of diseases such as arthritis, which has wide prospects of application in fields such as early diagnosis and efficacy evaluation of collagen-related diseases.