Fusion Protein Integrin Ligand Anti-Angiogenesis Specificity
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Solution Overview
Problem
Current anti-angiogenesis drugs like endostatin and angiostatin have poor target specificity and selectivity for blood vessels, leading to limited efficacy and high drug dosages required for treatment of tumors, arthritis, and ophthalmic diseases.
Innovation Solution
Development of a fusion protein combining an integrin αvβ3 ligand sequence, an antiangiogenesis polypeptide sequence, and an Fc sequence of an antibody IgG1, IgG2, or IgG4, linked by a flexible amino acid linker, which can form a correct high-order structure, enhancing affinity and stability, and prolonging half-life for targeted therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-angiogenesis drugs like endostatin and angiostatin are used, then they can inhibit angiogenesis, but they have poor target specificity and selectivity for blood vessels, leading to limited efficacy and high drug dosages required
Solution Approach 1:
The patent combines the integrin αvβ3 ligand sequence (which provides target specificity) with the anti-angiogenesis polypeptide sequence (which provides therapeutic effect) into a single fusion protein. This merging ensures that the drug specifically targets blood vessels while maintaining strong anti-angiogenesis activity, resolving the contradiction between target specificity and drug efficacy
Solution Approach 2:
The fusion protein is constructed as a composite molecular structure integrating two functional domains: the integrin αvβ3 ligand sequence that binds specifically to vascular endothelial cells, and the anti-angiogenesis polypeptide sequence that inhibits angiogenesis. This composite design achieves both high target specificity and potent therapeutic effect
2Reliability
If current anti-angiogenesis drugs are used, then they can inhibit angiogenesis, but high drug dosages are required for treatment
Solution Approach 1:
By merging the targeting function (integrin ligand) and therapeutic function (anti-angiogenesis polypeptide) into one fusion protein, the drug achieves potent anti-angiogenesis effects at lower dosages, eliminating the need for high drug quantities while maintaining reliable therapeutic effect
3Reliability
If a fusion protein is designed to improve target specificity, then affinity and stability are enhanced, but the structural complexity increases
Solution Approach 1:
The fusion protein merges two functional sequences into a single polypeptide chain connected by a flexible linker, creating a unified structure that simplifies production while maintaining high affinity and stability through the integrated design of the integrin ligand domain and anti-angiogenesis domain
Data Source
AI summary
The invention discloses a fusion protein, preparation method thereof and use thereof and belongs to the field of biopharmaceutical technology. The fusion protein according to the present invention has anti-tumor, anti-autoimmune diseases and anti-inflammatory functions, and therapeutic effects on ophthalmic diseases. According to the long-acting, multifunctional fusion protein of the present invention, the EDSM-Y or EDSM-X polypeptide is fused to the antibody immunoglobulin Fc fragment by a flexible linker so as to obtain the fusion proteins I-V, which can improve the efficacy, prolong the half-life and enhance stability, have characteristics of strong effect, low toxicity and the like, and can be used for the prevention and treatment of solid tumors and various types of inflammation and neovascular ophthalmic diseases. The fusion protein is expressed in a prokaryotic cell or a eukaryotic cell by a genetic engineering method, and the expressed fusion protein is obtained by affinity chromatography.