Modified VEGF-PlGF Fusion Protein for Stability and Productivity
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Solution Overview
Problem
Existing fusion proteins targeting vascular endothelial growth factors suffer from poor physicochemical properties, leading to reduced stability, non-specific binding, and degradation, which limits their effectiveness in treating cancer and angiogenesis-related diseases.
Innovation Solution
Modified fusion proteins with specific amino acid variations in the VEGFR1 domain D3, adjusted linkers, and disulfide bonds to enhance stability and persistence, improving binding affinity and production efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If fusion proteins are designed to target multiple vascular endothelial growth factors, then the efficacy against cancer and angiogenesis-related diseases is improved, but the physicochemical stability and productivity are reduced
Solution Approach 1:
The patent applies local quality by introducing specific amino acid substitutions at defined positions within the VEGFR1 D2-D3 domain structure. Rather than modifying the entire protein uniformly, targeted substitutions are made at specific residues (e.g., positions 238, 275, 282, 303, 329) to optimize local properties such as charge distribution and stability while preserving the overall multifunctional binding capability to VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PLGF
Solution Approach 2:
The patent employs parameter changes by systematically varying amino acid substitutions at specific positions to optimize the isoelectric point (pI) and charge variants of the fusion protein. By adjusting the net charge through substitutions like R238S, R275N, R282Q, and combinations thereof, the protein's physicochemical properties are tuned to improve stability and reduce non-specific binding while maintaining multifactor targeting
2Adaptability or versatility
If fusion proteins are designed to target multiple vascular endothelial growth factors, then the efficacy against cancer and angiogenesis-related diseases is improved, but the productivity and production efficiency are reduced
Solution Approach 1:
The patent applies local quality by introducing specific amino acid substitutions at defined positions within the VEGFR1 D2-D3 domain structure. Rather than modifying the entire protein uniformly, targeted substitutions are made at specific residues (e.g., positions 238, 275, 282, 303, 329) to optimize local properties such as charge distribution and stability while preserving the overall multifunctional binding capability to VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PLGF
Solution Approach 2:
The patent employs parameter changes by systematically varying amino acid substitutions at specific positions to optimize the isoelectric point (pI) and charge variants of the fusion protein. By adjusting the net charge through substitutions like R238S, R275N, R282Q, and combinations thereof, the protein's physicochemical properties are tuned to improve stability and reduce non-specific binding while maintaining multifactor targeting
3Duration of action of stationary object
If amino acid substitutions are introduced to improve stability, then the serum stability and persistence are improved, but the complexity of protein structure increases
Solution Approach 1:
The patent applies local quality by introducing specific amino acid substitutions at defined positions within the VEGFR1 D2-D3 domain structure. Rather than modifying the entire protein uniformly, targeted substitutions are made at specific residues (e.g., positions 238, 275, 282, 303, 329) to optimize local properties such as charge distribution and stability while preserving the overall multifunctional binding capability to VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PLGF
Solution Approach 2:
The patent employs parameter changes by systematically varying amino acid substitutions at specific positions to optimize the isoelectric point (pI) and charge variants of the fusion protein. By adjusting the net charge through substitutions like R238S, R275N, R282Q, and combinations thereof, the protein's physicochemical properties are tuned to improve stability and reduce non-specific binding while maintaining multifactor targeting
4Reliability
If amino acid substitutions are introduced to reduce non-specific binding, then the specificity is improved, but the manufacturing complexity increases
Solution Approach 1:
The patent applies local quality by introducing specific amino acid substitutions at defined positions within the VEGFR1 D2-D3 domain structure. Rather than modifying the entire protein uniformly, targeted substitutions are made at specific residues (e.g., positions 238, 275, 282, 303, 329) to optimize local properties such as charge distribution and stability while preserving the overall multifunctional binding capability to VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PLGF
Solution Approach 2:
The patent employs parameter changes by systematically varying amino acid substitutions at specific positions to optimize the isoelectric point (pI) and charge variants of the fusion protein. By adjusting the net charge through substitutions like R238S, R275N, R282Q, and combinations thereof, the protein's physicochemical properties are tuned to improve stability and reduce non-specific binding while maintaining multifactor targeting
Data Source
AI summary
The present disclosure relates to a modified fusion proteins in which a vascular endothelial growth factor is associated with a placental growth factor, and a use thereof. The modified fusion protein according to an embodiment of the present disclosure can exhibit excellent productivity and stability. The modified fusion protein according to an embodiment of the present disclosure can also demonstrate excellent blood stability. The modified fusion protein according to an embodiment of the present disclosure, compared to conventionally developed substances, possesses acidic properties and can show an increased ratio of charge isoforms in the acidic and neutral regions of the pI distribution.