Integrin alpha9beta1 Ligand Peptide EDDMMEVPY for High Affinity Binding
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Solution Overview
Problem
Current ligands for integrin α9β1, such as tenascin-C and osteopontin, have low binding affinities, and their functional roles as physiological ligands are uncertain, necessitating the identification of a novel ligand with higher affinity.
Innovation Solution
A peptide with the amino acid sequence EDDMMEVPY or its variants, derived from SVEP1, is identified as a ligand for integrin α9β1, which exhibits higher binding affinity and is used in various applications including cell culture, drug delivery, and stem cell regulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If known ligands (tenascin-C, osteopontin) are used for integrin α9β1, then cell adhesion activity can be measured, but binding affinity is markedly lower compared to other integrin-ligand interactions
Solution Approach 1:
The patent extracts the specific amino acid sequence EDDMMEVPY from the SVEP1 protein to create a minimal peptide ligand that specifically targets integrin α9β1. This extracted peptide sequence demonstrates high binding affinity while maintaining the essential ligand function, resolving the contradiction between using known ligands and achieving reliable high-affinity binding.
Solution Approach 2:
The invention focuses on the local amino acid sequence EDDMMEVPY within the larger SVEP1 protein as the critical binding region. By identifying and utilizing this specific local sequence, the patent creates a ligand with optimized binding properties for integrin α9β1, achieving both high affinity and physiological relevance.
2Reliability
If full-length ECM proteins (tenascin-C, osteopontin) are used as ligands, then ligand activity can be detected in specific fragments, but it remains uncertain whether they function as physiological ligands
Solution Approach 1:
The patent extracts the essential binding sequence EDDMMEVPY from the complex full-length SVEP1 protein. This extracted peptide maintains the physiological ligand function while eliminating the complexity of the full protein structure, providing a simplified yet functional ligand for integrin α9β1.
Solution Approach 2:
The invention segments the large SVEP1 protein into a smaller functional unit by identifying and utilizing the specific EDDMMEVPY sequence. This segmentation approach preserves the essential ligand activity while reducing structural complexity, making it suitable for physiological function studies.
3Measurement precision
If cell adhesion activity is used to measure ligand function, then integrin α9β1-binding activity can be assessed, but direct binding affinity measurement is not achieved
Solution Approach 1:
The patent extracts the core binding sequence EDDMMEVPY from SVEP1 to create a simplified peptide ligand. This extracted peptide enables direct binding affinity measurements through its specific interaction with integrin α9β1, providing precise measurement capability while maintaining ease of operation through the simplified peptide structure.
Data Source
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AI summary
Provided is a novel ligand for integrin α9β1 consisting of a peptide having the following amino acid sequence: (A) EDDMMEVPY (SEQ ID NO: 1) or (B) an amino acid sequence the same as the amino acid sequen ce represented by SEQ ID NO: 1 except for having deletion, s ubstitution or addition of 1 to 3 amino acids. The novel lig and for integrin α9β1 has a higher binding affinity than tho se of tenascin-C and osteopontin, which are known ligands fo r integrin α9β1.