FGFR-Binding Cyclic Peptide with Stable Thioether Cyclization
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Solution Overview
Problem
Existing cyclic peptides with FGFR binding affinity are unstable and have low binding efficacy, making them impractical for cell culture applications, particularly in the production of cultured meat where growth factors like bFGF are costly and unstable.
Innovation Solution
Development of a cyclic peptide with specific amino acid residues at specific positions in the sequence, forming a cyclized structure via covalent bonding, which exhibits high binding affinity to the FGFR protein, enhancing stability and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a disulfide-type cyclic peptide is used to bind to FGFR, then binding affinity is achieved, but the peptide is unstable and easily decomposed in cell culture environment
Solution Approach 1:
The invention changes the chemical nature of the cyclized portion from disulfide bond to thioether bond, altering the chemical parameters to achieve both stability and binding affinity. This parameter change transforms the unstable disulfide linkage into a stable thioether linkage while preserving the cyclic structure's ability to bind FGFR.
Solution Approach 2:
The invention creates a composite peptide structure combining linear peptide segments with a cyclized portion containing thioether bond. This composite structure integrates the stability of thioether chemistry with the binding functionality of the cyclic conformation, achieving both reliability and stability.
2Productivity
If conventional growth factors like bFGF are used to promote cell proliferation, then cell proliferation and undifferentiated potency maintenance are achieved, but the cost is extremely high and stability is low
Solution Approach 1:
The invention creates a simplified copy or analog of the natural bFGF growth factor function using a cyclic peptide structure. Instead of using the complex and expensive natural bFGF protein, the cyclic peptide replicates the essential binding and proliferative effects at a fraction of the cost, making cell culture economically viable.
Solution Approach 2:
The cyclic peptide serves as a cost-effective alternative to expensive natural growth factors. By using this synthetic peptide, the invention enables the use of disposable or single-use cell culture systems without incurring the high recurring costs of natural growth factor procurement and storage.
3Stability of the object's composition
If a thioether-type cyclic peptide is used to improve stability, then stability is achieved, but binding affinity to FGFR is significantly low
Solution Approach 1:
The invention applies local quality by specifically positioning certain amino acid residues at key locations within the cyclic structure. By optimizing the local sequence composition and arrangement, the peptide maintains high binding affinity to FGFR while the thioether bond provides overall structural stability.
Solution Approach 2:
The invention creates a dynamic balance between structural stability and binding flexibility. The thioether bond provides rigid structural framework for stability, while the amino acid side chains maintain dynamic flexibility to adapt to the FGFR binding interface, achieving both stability and high affinity.
Data Source
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AI summary
An object of the present invention is to provide a cyclic peptide or a salt thereof and a cyclic peptide complex or a salt thereof, which have excellent binding affinity to an FGFR protein, and to provide a culture medium composition, a material for purification, a material for labeling, a material for cell regulation, and a material for accumulation, which use the cyclic peptide or a salt thereof and the cyclic peptide complex or a salt thereof. According to the present invention, there is provided a cyclic peptide or a salt thereof, the cyclic peptide being a peptide having an amino acid sequence represented by X1-Xm-X2-Xn-X3, in which the cyclic peptide contains a cyclized portion that is cyclized via covalent bonding, and the cyclized portion includes a structure represented by Formula (2), X1 represents a glutamine residue or a histidine residue, Xm represents a peptide residue containing any 2 to 4 amino acid residues, X2 represents an alanine residue, a leucine residue, an isoleucine residue, a phenylalanine residue, a tyrosine residue, a tryptophan residue, a glutamine residue, a serine residue, a threonine residue, an asparagine residue, a glutamic acid residue, an arginine residue, or a histidine residue, Xn represents an amino acid residue or a peptide residue containing any 1 to 3 amino acid residues, and X3 represents an amino acid residue containing an aromatic residue on a side chain, in Formula (2), Z1 and Z2 each independently represent a linking group, and m represents an integer of 1 to 10.