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, impacting the economic viability of cell therapy products.
Innovation Solution
Development of a cyclic peptide with specific amino acid sequences and structures, such as those represented by Formulas (1) and (2), which exhibit high binding affinity and stability to the FGFR protein, enabling their use in culture media compositions, additives, and materials for purification, labeling, cell regulation, and accumulation.
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 poor due to easy decomposition of the disulfide bond in cell culture environment
Solution Approach 1:
The patent changes the chemical structure parameter by replacing the disulfide bond with a thioether bond, transforming the cyclic peptide from a disulfide-type to a thioether-type structure. This structural modification maintains binding affinity while significantly improving stability against decomposition in cell culture environments.
Solution Approach 2:
The patent creates a composite cyclic peptide structure combining specific amino acid sequences (X1-X2-X3-X4) with a thioether linkage, integrating the binding functionality of the peptide sequence with the stability-enhancing thioether bond structure.
2Stability of the object's composition
If the amino acid sequence from WO 2000/003245A is combined with the stable thioether bond from JP 2017-95443A, then stability is improved, but binding affinity to FGFR protein becomes significantly low
Solution Approach 1:
The patent applies local quality by carefully selecting and positioning specific amino acid residues (X1-X2-X3-X4) at critical positions in the cyclic peptide structure. The sequence X1(X2)(X3)X4 where X2 is aromatic and X1/X4 are aliphatic creates a local structural motif that optimizes both binding affinity to FGFR and stability through the thioether bond.
3Reliability
If conventional growth factors like bFGF are used in cell culture media, then cell proliferation and undifferentiated potency are maintained, but manufacturing costs become excessively high
Solution Approach 1:
The patent develops a synthetic cyclic peptide that serves as a cost-effective alternative to expensive conventional growth factors. The peptide can be produced through chemical synthesis rather than requiring costly cell culture systems, significantly reducing manufacturing costs while maintaining functional activity in promoting cell proliferation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The cyclic peptides demonstrate excellent binding affinity and stability to FGFR proteins, enhancing cell proliferation and maintaining undifferentiated potency, thereby reducing costs and improving the efficiency of cell culture processes.
Implementation Method 1
a cyclic peptide having an amino acid sequence represented by X1-X2-X3-X4, in which the cyclic peptide contains a cyclized portion that is cyclized via covalent bonding
Implementation Method 2
the cyclized portion includes a structure represented by Formula (2)... cyclized via covalent bonding
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-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 leucine residue, an isoleucine residue, a valine residue, a phenylalanine residue, a tyrosine residue, or a threonine residue, X2 represents an amino acid residue having an aromatic residue on a side chain, X3 represents any amino acid residue, and X4 represents an alanine residue, a glycine residue, a phenylalanine residue, a tyrosine residue, a tryptophan residue, a serine residue, or a histidine residue, in Formula (2), Z1 and Z2 each independently represent a linking group, and m represents an integer of 1 to 10.