Functional Moieties for Macromolecule Stability and Toxicity Reduction
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Solution Overview
Problem
Unmodified macromolecules, including oligonucleotides, possess poor therapeutic properties such as low stability, specificity, and high toxicity, leading to off-target effects, limiting their pharmaceutical applications.
Innovation Solution
Development of functional moieties and bioconjugate linkers that can be chemically, thermally, or photo-cleavable, linked to solid supports, enhancing the stability, binding affinity, and cellular uptake of macromolecules, and reducing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If unmodified macromolecules are used for therapeutic applications, then simplicity of use is maintained, but stability is poor and toxicity is high
Solution Approach 1:
The patent applies composite materials by combining macromolecules with functional moieties to create hybrid structures. These composites include macromolecules conjugated with cell-penetrating moieties, targeting moieties, or imaging moieties, thereby improving stability and therapeutic properties while maintaining the core macromolecule structure.
Solution Approach 2:
The patent segments the therapeutic agent into multiple functional components: the macromolecule core, cell-penetrating moieties for cellular uptake, targeting moieties for specific localization, and imaging moieties for tracking. This segmentation allows each component to perform its specific function independently, improving overall stability and reducing toxicity.
2Reliability
If functional moieties are added to improve therapeutic properties, then stability and specificity are improved, but complexity of the compound increases
Solution Approach 1:
The patent employs universal functional moieties that can be conjugated to various macromolecules to impart multiple functions simultaneously. For example, a single functional moiety can provide both cell-penetrating capability and targeting specificity, reducing the need for multiple separate modifications and thereby limiting complexity increase.
Solution Approach 2:
The patent applies local quality by placing specific functional moieties at particular locations on the macromolecule structure. Targeting moieties are positioned to recognize specific cellular receptors, while cell-penetrating moieties are placed to facilitate membrane crossing, ensuring each region of the compound has the appropriate function without unnecessary complexity elsewhere.
3Object-affected harmful factors
If macromolecules are functionalized to reduce toxicity, then safety is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-conjugating functional moieties to macromolecules during the synthesis process rather than adding them afterward. Solid-phase synthesis methods are used to incorporate cell-penetrating and targeting moieties into the macromolecule structure during assembly, reducing the need for separate toxicological modification steps and simplifying manufacturing.
Solution Approach 2:
The patent uses linkers as intermediaries to connect macromolecules with functional moieties. These linkers provide stable, controlled conjugation points that reduce unwanted side reactions and simplify purification processes, thereby reducing manufacturing complexity while maintaining low toxicity through precise functional moiety placement.
Data Source
AI summary
Provided herein are functional moieties, functionalized compounds and macromolecules, their preparation, and uses thereof.