NOTA-Based Chelating Agents for Selective Copper Removal
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Solution Overview
Problem
Current treatments for neurodegenerative diseases like Wilson's and Alzheimer's, and metal ion poisoning lack selective and less toxic chelating agents that can effectively manage intracellular copper accumulation and reduce severe side effects.
Innovation Solution
Development of new compounds derived from 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) with phenylalanine or tryptophan residues, and NTA carrying glycine, leucine, phenylalanine, or aspartic acid, which are synthesized through specific reaction steps involving cysteine derivatives and deprotection of thiol functions, providing enhanced selectivity and reduced toxicity for chelating metal ions like copper and zinc.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing chelating agents like D-penicillamine are used to increase copper excretion, then copper removal effectiveness is improved, but severe side effects occur including mucocutaneous reactions, hematological issues, and renal problems
Solution Approach 1:
The patent modifies the chemical structure of chelating agents by incorporating specific amino acid residues (phenylalanine, tryptophan, glycine, leucine, or aspartic acid) into the NOTA and NTA frameworks. These structural parameter changes create new compounds with altered chelating properties that maintain copper removal effectiveness while reducing toxicity and side effects compared to conventional agents like D-penicillamine
Solution Approach 2:
The invention creates composite chelating agents by combining the NOTA or NTA core structure with specific amino acid residues. This composite approach integrates the copper-chelating capability of the macrocyclic framework with the biocompatibility and selectivity enhancements provided by the amino acid side chains, resulting in a agent that achieves both effectiveness and reduced harm
2Reliability
If non-selective chelating agents like Trien and EDTA are used, then copper chelation capability is improved, but selectivity for intracellular copper is lost and other metal ions are also chelated
Solution Approach 1:
The patent introduces local quality differences by incorporating specific amino acid residues at particular positions on the NOTA or NTA framework. These localized modifications create specific binding sites with tailored properties that enhance selectivity for intracellular copper ions while maintaining overall chelation capability. The amino acid side chains provide localized chemical environments that discriminate between different metal ions
3Duration of action of stationary object
If lifetime treatment with chelating medications is administered, then copper accumulation is controlled, but treatment complexity and monitoring requirements increase
Solution Approach 1:
The new chelating agents are designed to be more biocompatible and less toxic, allowing them to function effectively over extended periods without requiring intensive medical monitoring. The compounds' improved safety profile enables a form of self-service treatment where the medication can be administered long-term with reduced need for complex monitoring protocols and medical intervention, making lifetime management more sustainable
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
These compounds demonstrate improved selectivity and reduced toxicity, effectively chelating intracellular copper and other metal ions, offering a better alternative for diagnosis, prevention, and treatment of neurodegenerative diseases with fewer side effects compared to existing agents.
Implementation Method 1
new compounds of formula (I) capable of being used as metal ion chelating agents
Data Source
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AI summary
The invention relates to compounds that can be used as metal ion chelating agents or as pollution control agents, having general formula (I), to precursor compounds having formula (II) and to labeled compounds having formula (III). The present invention also relates to the use of compounds (I), (II) or (III) as drugs and to the use thereof for diagnosing, preventing and treating neurodegenerative diseases such as Wilson's disease and Alzheimer's disease.