Cleavable Linkers for Intracellular Target Capture and Release
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Solution Overview
Problem
Current techniques for detecting, isolating, and immobilizing cells, proteins, and molecules are limited in efficiency and compatibility within biological environments, particularly in terms of cell permeability and chemoselective cleavage.
Innovation Solution
Development of cell-permeable, cell-compatible, and chemoselectively-cleavable linkers that tether functional elements, such as cellular interaction and capture elements, allowing for intracellular binding and extracellular release of cellular targets using chemoselectively-cleavable moieties like allyl-heteroatom and propargyl-containing linkers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional linkers are used for tethering functional elements, then detection and isolation can be performed, but cell permeability is limited and cellular compatibility is reduced
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of linkers to include cell-permeable and cell-compatible moieties. Specifically, the linkers are designed with hydrophobic and hydrophilic regions that enable them to traverse cell membranes while maintaining stability in cellular environments, thus improving both cell permeability and detection efficiency simultaneously
Solution Approach 2:
The patent employs composite materials by creating linkers that combine multiple functional groups within a single molecular structure. These composite linkers integrate cell-penetrating peptides, cleavable moieties, and tethering functional elements, allowing them to perform multiple functions (permeation, stability, and target binding) within a single component, thereby resolving the contradiction between reliability and productivity
2Stability of the object's composition
If stable covalent bonds are used for tethering, then immobilization is achieved, but selective release and cleavage become difficult
Solution Approach 1:
The patent applies segmentation by dividing the linker into distinct functional modules: a stable tethering region that provides immobilization and a separate cleavable moiety that enables selective release. This modular design allows the bond to remain stable during immobilization while permitting controlled breakdown when needed, resolving the contradiction between stability and ease of release
Solution Approach 2:
The patent implements dynamics by designing linkers with conditionally stable bonds that can transition from a stable state (for immobilization) to a labile state (for release). The cleavable moieties are engineered to respond to specific stimuli (such as light, pH, or enzymatic activity), allowing the bond strength to be dynamically adjusted based on operational requirements, thus achieving both stable tethering and selective release
3Measurement precision
If existing detection methods are used, then molecular detection is possible, but damage to cellular environment occurs
Solution Approach 1:
The patent applies mechanics substitution by replacing harsh chemical or physical detection methods with gentler, more selective techniques. The linkers are designed to enable detection through specific molecular recognition events (such as fluorescence resonance energy transfer or enzymatic activity) that occur under physiological conditions, eliminating the need for damaging mechanical or chemical disruption while maintaining high detection precision
Solution Approach 2:
The patent employs intermediaries by using the linker molecules themselves as mediators between the detection system and the cellular targets. These linkers are designed to be non-toxic and biocompatible, allowing them to bridge the detection mechanism and cellular components without causing damage to the cellular environment, thus achieving precise measurement while protecting cellular integrity
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 efficient labeling, detection, isolation, and immobilization of cellular targets with minimal damage to the cellular environment, maintaining cell compatibility and allowing for selective release of bound targets.
Implementation Method 1
chemoselectively-cleavable linkers for connecting molecular entities and/or functional elements
Data Source
AI summary
Provided herein are cell-permeable, cell-compatible, and chemoselectively-cleavable linkers for tethering (e.g., covalently) functional elements (e.g., a cellular interaction element and a capture element), and methods of use (e.g., intracellular capture and extracellular release of cellular targets) therewith.