Partially Unfolded Polypeptide Complexes for Tumor-Selective Ion Channel Activation
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Solution Overview
Problem
Current cancer therapies lack specificity, leading to side effects due to non-targeted ion channel modulation, and there is a need for more effective ways to selectively target and kill cancer cells while sparing healthy cells.
Innovation Solution
Development of biologically active complexes comprising partially unfolded polypeptides, such as variants of α-lactalbumin or lysozyme, combined with pharmaceutically acceptable salts of fatty acids or lipids, which selectively activate ion channels in tumor cells, leading to cell death and immune response activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies modulate ion channels, then therapeutic effect is achieved, but specificity is lost leading to side effects
Solution Approach 1:
The patent applies local quality by creating a complex with specific spatial arrangement where a polypeptide is bound to a fatty acid at a particular location. This localized binding creates a specific conformational state that enables selective interaction with ion channels in tumor cells versus healthy cells, providing the needed specificity to reduce side effects while maintaining therapeutic efficacy.
Solution Approach 2:
The patent utilizes parameter changes by altering the conformational state of the polypeptide through fatty acid binding. This changes physical parameters such as protein folding state, charge distribution, and molecular shape, which in turn modifies the interaction properties with ion channels to achieve tumor-selective targeting.
2Adaptability or versatility
If ion channels are modulated non-specifically, then broad therapeutic coverage is achieved, but tumor selectivity is reduced
Solution Approach 1:
The patent employs composite materials by combining a polypeptide with a fatty acid to form a biologically active complex. This composite structure integrates the properties of both components - the polypeptide provides ion channel interaction capability while the fatty acid induces specific conformational changes - resulting in a molecule with both broad therapeutic coverage and high tumor selectivity.
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 complexes demonstrate tumor-specific ion channel activation, inducing cell death in carcinoma cells while sparing healthy cells, with reduced toxicity and enhanced therapeutic efficacy by triggering a beneficial innate immune response.
Implementation Method 1
biologically active complexes comprising partially unfolded polypeptides, such as variants of α-lactalbumin or lysozyme, combined with pharmaceutically acceptable salts of fatty acids or lipids
Implementation Method 2
Ion channels are membrane proteins that sense alterations in membrane tension or cellular environment, and their activation has been proposed to catalyze several signaling cascades
Data Source
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AI summary
Biologically active complex and its preparation A biologically active complex comprising either a polypeptide having the sequence of a variant of a naturally occurring protein, wherein said polypeptide is at least partially unfolded as compared to the said naturally occurring protein; or a peptide of up to 50 amino acids, for instance a fragment of the naturally occurring protein or a variant thereof; and a pharmaceutically acceptable salt of a fatty acid or lipid. The complexes of the invention demonstrate a novel mode of action, that gives rise to opportunities for the development of further active agents and screening methods.