Drug Target Capturing via Covalent Nucleic Acid Linking
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Solution Overview
Problem
Current methods for capturing drug targets are inefficient due to the complexity of cellular signaling pathways and the difficulty in maintaining protein conformations during cell lysis, leading to false positive results and restricted drug application.
Innovation Solution
Compounds are covalently linked to DNA or RNA and transferred into cells using specific gene transfer methods, allowing for binding with targets in their native conformation, followed by enrichment and identification using immobilized complementary nucleic acids or affinity materials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If cell lysis is performed to capture drug targets, then drug targets can be accessed, but proteins lose their native conformation leading to false positive results
Solution Approach 1:
The patent applies preliminary action by performing the drug-target binding event before cell lysis. Drugs are introduced to living cells first, allowing them to bind to their native targets while maintaining proper protein conformations and cellular environments. Only after this binding occurs is the cell lysis performed to release and capture the drug-target complexes, thereby preserving the physiological relevance of the interactions.
2Stability of the object's composition
If the cell membrane is intact to maintain physiological state, then protein conformations are preserved, but drugs with low membrane permeability cannot enter cells
Solution Approach 1:
The patent performs the drug delivery action before disrupting the cell membrane. Drugs are introduced to intact living cells first, allowing them to enter through natural membrane transport mechanisms and bind to targets in the physiological environment. The cell lysis step is delayed until after binding occurs, thus preserving both the membrane barrier function during drug delivery and the protein conformations during target capture.
3Measurement precision
If cell lysis is performed to access intracellular targets, then all proteins are mixed together, but this creates false positives by allowing drugs to act on targets not accessible in normal physiological state
Solution Approach 1:
The patent performs drug-target binding in living cells before lysis, allowing the complex cellular signaling pathways and compartmentalization to naturally regulate which drugs can access which targets. The cell membrane and organelle structures remain intact during the binding phase, ensuring that only physiologically relevant interactions occur. Subsequent lysis then captures these pre-established complexes without creating false positives.
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
This method enables the capture of drug targets in a more physiological state, reducing false positives and improving the accuracy of drug target identification, while allowing compounds with low membrane permeability to act effectively within cells.
Implementation Method 1
Covalently linking the compounds to the DNA or RNA or the one party of other specific affinity materials, to obtain labeled compounds
Implementation Method 2
Transferring: transferring the labeled compounds obtained in the step (2) into cells by a specific gene transfer method
Implementation Method 3
capturing the DNA or RNA in the step (1) by immobilized complementary DNA or RNA, or capturing the one party of affinity materials in the step (1) by the other party of immobilized specific affinity materials
Data Source
AI summary
The present invention discloses a method for capturing drug targets, comprising the following steps of: (1) preparing row materials, i.e., compounds and DNA or RNA or one party of other specific affinity materials; (2) linking: covalently linking the compounds to the DNA or RNA or the one party of other specific affinity materials, to obtain labeled compounds; (3) transferring: transferring the labeled compounds obtained in the step (2) into cells by a specific gene transfer method; (4) capturing targets: disrupting the cells in the step (3), and then capturing the DNA or RNA in the step (1) by immobilized complementary DNA or RNA, or capturing the one party of affinity materials in the step (1) by the other party of immobilized specific affinity materials, thus to enrich the targets through the covalently linked labeled compounds and the affinity of the targets; (5) identifying targets: dissociating the enriched targets from a stationary phase, deploying the targets by a gel electrophoresis method or by an equivalent separation method, and comparing differential proteins by proteomics thus to identify the potential targets; and (6) determining targets: expressing or purchasing the targets identified in the step (5) by priority, and comparing by interaction of the compounds with those targets one by one to determine the targets for the compounds. By the method of the present invention, compounds with low membrane permeability may be transferred into cells to be bound with the targets in the cells, to realize the target identification closer to the real physiological environment and thus provide more conclusive evidences for the acting mechanism of the compounds to diseases. Additionally, the method for capturing drug targets of the present invention is novel, easy, efficient, and low in cost, and has good application prospects.