Thioether-Cyclized RGD Peptides for Stable Integrin Binding
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Solution Overview
Problem
Existing cyclic peptides exhibit low molecule stability, particularly in terms of alkali resistance, acid resistance, and resistance to actinic rays, which affects their integrin binding properties and longevity in applications such as cell culture scaffolds and separation materials.
Innovation Solution
A cyclic peptide with a specific amino acid sequence crosslinked by thioether bonds, retaining an RGD sequence in nested cyclic moieties, enhancing molecule stability and integrin binding properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cyclic peptides are designed with high integrin binding properties using conventional methods, then integrin binding affinity is improved, but molecule stability deteriorates
Solution Approach 1:
The patent changes the chemical parameter of the peptide bond by introducing thioether bonds (S-alkyl bonds) instead of conventional disulfide bonds or simple cyclic structures. This parameter change in bond type and chemical composition achieves both high integrin binding affinity through the RGD sequence and enhanced molecule stability through the unique thioether linkage that resists degradation.
Solution Approach 2:
The patent creates a composite cyclic peptide structure combining multiple amino acid residues (Arginine-Glycine-Aspartic acid RGD sequence) with thioether crosslinks. This composite approach integrates the integrin-binding RGD motif with stabilizing thioether bonds, achieving both high binding affinity and enhanced molecular stability that neither component could achieve alone.
2Duration of action of stationary object
If cyclic peptides are designed for long-term application, then duration of action is improved, but molecule stability deteriorates due to degradation
Solution Approach 1:
The patent changes the chemical stability parameter by using thioether bonds which are chemically more stable and resistant to degradation compared to conventional peptide bonds or disulfide bonds. This parameter change enables the cyclic peptide to maintain its structure and function over extended periods, achieving both long-term effectiveness and resistance to degradation.
3Ease of manufacture
If conventional cyclic peptide structures are used, then ease of manufacture is improved, but molecule stability deteriorates in alkali resistance
Solution Approach 1:
The patent changes the chemical composition parameter by incorporating thioether crosslinked amino acid residues that provide alkali resistance. The thioether bond (C-S-C linkage) is chemically stable in alkaline conditions, unlike disulfide bonds which are susceptible to reduction in alkaline environments. This parameter change achieves both ease of manufacture through established peptide synthesis methods and improved alkali resistance.
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 peptide demonstrates improved alkali resistance and integrin binding stability, enabling effective use in cell culture scaffolds and separation materials over extended periods.
Implementation Method 1
Xa and Xb, and Xc and Xd each independently represent amino acid residues crosslinked through a thioether bond
Data Source
AI summary
There is provided a cyclic peptide having an amino acid sequence represented Formula (1). In the formula, Xa and Xb, and Xc and Xd each independently represent amino acid residues crosslinked through a thioether bond; X1 to X5 each independently represent an amino acid residue; R represents an arginine residue; G represents a glycine residue; D represents an aspartic acid residue; and m1 to m5 each independently represent an integer of 0 or more. However, the total number of amino acid residues represented by Xa, Xb, Xc, and Xd and represented by X1, X3, and X4 is 7 to 16.