Surface Immobilized Chaperones via Molecular Linkers
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Solution Overview
Problem
Existing containers for pharmaceutical proteins face challenges in preventing the unfolding and misfolding of proteins due to contact with surfaces, leading to inactivation and aggregation, which is not effectively addressed by prior methods that immobilize chaperones using chemical reactions that alter their native conformation.
Innovation Solution
A container with an inner surface coated using molecular linkers that interpose between the surface and chaperones, preventing the release of chaperones into the solution and maintaining their activity by using pre-adsorbed unfolded proteins as linkers, which are bound to the surface through non-covalent interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chaperones are immobilized on a solid surface by chemical reactions forming covalent bonds, then chaperones are prevented from releasing free in solution, but disulfide bridges are destroyed and chaperones may lose their native conformation and activity
Solution Approach 1:
The patent introduces a molecular linker as an intermediary component between the solid surface and the chaperone protein. This linker forms covalent bonds with the surface while the chaperone binds to the linker through non-covalent interactions, thereby preventing direct covalent bonding that would destroy disulfide bridges and maintain the chaperone's native conformation and activity.
2Reliability
If chaperones are free in the pharmaceutical solution, then they can contribute to the refolding of unfolded proteins, but chaperones may be released and cause unwanted effects
Solution Approach 1:
The molecular linker serves as an intermediary that anchors the chaperone to the container surface, preventing its release into the pharmaceutical solution. This allows the chaperone to remain positioned where it can assist protein refolding while avoiding the harmful effects of free chaperone circulation in the solution.
Solution Approach 2:
The patent extracts the chaperone from the bulk solution phase and immobilizes it on the container surface through the molecular linker. This separation allows the chaperone to exert its beneficial refolding effect locally at the surface while preventing its unwanted presence in the solution phase.
3Ease of manufacture
If chemical reactions are used to bind chaperones to the surface, then immobilization is achieved, but the chemical modification alters chaperone structure and reduces activity
Solution Approach 1:
The molecular linker acts as a mediator that undergoes chemical modification to bind to the surface, while the chaperone itself only experiences non-covalent binding to the linker. This separation of chemical and physical binding steps simplifies the manufacturing process while preserving chaperone activity.
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 effectively prevents protein aggregation and maintains chaperone activity by using pre-adsorbed unfolded proteins as molecular linkers, ensuring the stability and efficacy of therapeutic proteins during storage and administration.
Implementation Method 1
pre-adsorbed unfolded proteins as linkers, which are bound to the surface through non-covalent interactions
Implementation Method 2
chaperones coupled to the inner surface by a molecular linker—the linker being interposed between the surface of the container and the chaperone
Data Source
AI summary
A container containing a therapeutic protein, characterized in that chaperones molecules are bound by a molecular linker to an inner surface of the container. The linker being interposed between the surface and the chaperone.