FGFR-Binding Cyclic Peptide Composition 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 use in cell culture media and cell therapy products, particularly due to the high cost and instability of growth factors like bFGF.
Innovation Solution
Development of a cyclic peptide with specific amino acid sequences and covalent bonding structures, such as Formula (2), which exhibit high binding affinity and stability to FGFR proteins, and can be used in culture media compositions, additives, purification materials, and cell regulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a disulfide-type cyclic peptide is used to bind to FGFR protein, then binding affinity is achieved, but stability is significantly reduced due to easy decomposition of the disulfide bond
Solution Approach 1:
The patent changes the chemical bond type from disulfide bond to thioether bond, altering the chemical parameters to achieve both high binding affinity and high stability. The thioether bond provides resistance to decomposition while maintaining the ability to bind to FGFR protein, thus resolving the contradiction between reliability and stability.
Solution Approach 2:
The patent creates a composite cyclic peptide structure that combines specific amino acid sequences with thioether bonding. This composite structure integrates the binding functionality with the stability requirement, achieving both high affinity for FGFR and resistance to decomposition in cell culture environments.
2Reliability
If basic FGF is used to promote cell proliferation and maintain undifferentiated potency, then cell therapy quality is improved, but manufacturing cost increases significantly
Solution Approach 1:
The patent replaces expensive basic FGF with a cyclic peptide that has similar biological functions but lower cost. The cyclic peptide can be synthesized more economically and provides comparable effects in promoting cell proliferation and maintaining undifferentiated potency, thus reducing manufacturing costs while maintaining therapy quality.
Solution Approach 2:
The patent creates a cyclic peptide that copies the essential binding functionality of basic FGF to FGFR protein. By replicating the key interaction mechanism without using the expensive natural growth factor, the invention achieves similar therapeutic effects at lower cost.
3Productivity
If growth factor is used as a component in cell culture medium, then cell proliferation is promoted, but production cost increases due to high expense and low stability of growth factor
Solution Approach 1:
The patent substitutes expensive and unstable growth factors with a stable cyclic peptide that can be synthesized at lower cost. The cyclic peptide maintains the ability to promote cell proliferation while being more cost-effective and stable in culture conditions, thus improving productivity while reducing manufacturing costs.
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 excellent stability, 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. A cyclic peptide or a salt thereof, the cyclic peptide being a peptide having an amino acid sequence represented by X1-Xn-X2-X3-X4, 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 an alanine residue, a proline residue, a leucine residue, an isoleucine residue, a valine residue, a phenylalanine residue, a tyrosine residue, a tryptophan residue, an asparagine residue, a serine residue, an arginine residue, a histidine residue, or a methionine residue, Xn represents a peptide residue containing any 1 to 7 amino acid residues, X2 represents an alanine residue, a glycine residue, a leucine residue, an isoleucine residue, or a valine residue, X3 represents any amino acid residue, and X4 represents an amino acid residue having 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.