Redox-Activated Pro-Chelators for Selective Intracellular Metal Sequestration
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Solution Overview
Problem
Current treatments for conditions associated with metal ion dysregulation, such as cancer, lack selective and targeted chelation strategies that can effectively manage metal ion levels within cells.
Innovation Solution
Development of redox-activated pro-chelators with a reducible disulfide bond that transform into high-affinity chelators under reducing conditions, specifically designed to sequester iron and other metals, thereby addressing metal ion dysregulation in conditions like cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional chelators are used to treat metal ion dysregulation, then metal ion levels can be managed, but the treatment lacks selectivity and targeting capability for specific cellular locations
Solution Approach 1:
The chelating agent is segmented into two distinct components: a pro-chelator moiety that can cross cell membranes and a disulfide bond linkage. This segmentation allows the therapeutic agent to be delivered to the target location (intracellular space) before activation, providing both selectivity for the disease location and versatility in mechanism of action
Solution Approach 2:
The pro-chelator is administered in its inactive form first, allowing it to be taken up by cells through membrane transport. The active chelating function is then unleashed only after the disulfide bond is reduced intracellularly, performing the chelation action at the precise location and time needed, thus achieving both selectivity and targeting capability
2Reliability
If high-affinity chelators are administered directly to sequester metal ions, then metal ion sequestration is effective, but the treatment cannot selectively target intracellular metal ions without affecting extracellular levels
Solution Approach 1:
The disulfide bond serves as an intermediary mechanism that connects the extracellular administration route with intracellular activation. The pro-chelator crosses the cell membrane in its stable form, and the disulfide bond reduction acts as the intermediary step that triggers activation only inside the cell, thereby achieving selective intracellular targeting while maintaining effective metal ion sequestration
Solution Approach 2:
The chemical state of the chelator changes from reduced (inactive pro-chelator form) to oxidized (active chelator form) through disulfide bond reduction. This parameter change occurs specifically within the cellular environment, allowing the same molecule to be administered systemically but activated selectively intracellularly, achieving both effective sequestration and selective targeting
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 redox-activated pro-chelators effectively target and sequester metal ions, providing a selective and effective treatment for conditions associated with metal ion dysregulation, including cancer, by releasing high-affinity chelators that stabilize iron centers and inhibit cell proliferation.
Implementation Method 1
pro-chelators which can be activated in reducing conditions so as to transform into chelators that sequester iron or another metal
Implementation Method 2
redox-activated pro-chelators having a reducible disulfide bond that transform into high-affinity chelators under reducing conditions
Implementation Method 3
transform into chelators that sequester iron or another metal
Data Source
AI summary
Compositions of pro-chelator compounds are described herein. The pro-chelators may be activated in reducing conditions, such as in the intracellular space, so as to sequester metals such as iron. The pro-chelators may be used to target malignant cells or in the treatment in a condition associated with metal ion disregulation.