Cyclic Peptide Thiazoline Cyclization for Membrane Permeability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for producing cyclic peptides with high membrane permeability and target-binding ability are limited, and there is a need for a method to select peptide compounds that effectively bind to target substances.
Innovation Solution
A novel peptide compound represented by General Formula (1) or its salt, produced by reacting an amino acid with a cyano group and an amino acid having a reactive group like cysteine in a cell-free translation system, is used to create a cyclic peptide library with enhanced cell membrane permeability and target-binding capability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Shape
If thioether cyclization method or triazole cyclization method is used to produce cyclic peptide compound, then cyclic structure is formed, but membrane permeability and target-binding ability are limited
Solution Approach 1:
The patent introduces a novel cyclization method using a cyano group-containing amino acid that reacts with a cysteine residue to form a thiazoline ring. This chemical reaction pathway (parameter change) produces cyclic peptides with superior membrane permeability and target-binding ability compared to conventional thioether or triazole cyclization methods, directly resolving the contradiction between cyclic structure formation and functional performance
2Reliability
If peptide compound is designed for high target-binding ability, then binding affinity increases, but cell membrane permeability decreases
Solution Approach 1:
The patent employs a specific chemical reaction mechanism where a cyano group-containing amino acid reacts with cysteine to form a thiazoline ring structure. This structural parameter change creates a unique cyclic peptide conformation that simultaneously achieves high target-binding affinity and excellent cell membrane permeability, overcoming the traditional trade-off between these two properties
3Adaptability or versatility
If cyclic peptide library is constructed using existing methods, then library diversity is achieved, but production efficiency and metabolic stability are insufficient
Solution Approach 1:
The patent utilizes a cell-free translation system that autonomously synthesizes cyclic peptides containing cyano group-containing amino acids and cysteine residues. The system self-assembles the cyclic structure through the inherent chemical reactivity between the cyano group and cysteine thiol group, eliminating the need for complex external cyclization chemistry and significantly improving production efficiency and metabolic stability while maintaining library diversity
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 peptide compound exhibits excellent cell membrane permeability and metabolic stability, facilitating the construction of a cyclic peptide library for effective target binding.
Implementation Method 1
a cyclic peptide can be produced by reacting an amino acid having a cyano group with an amino acid represented by General Formula (2) (an amino acid having a reactive group such as cysteine) in a cell-free translation system
Data Source
AI summary
An object of the present invention is to provide a novel cyclic peptide compound excellent in cell membrane permeability, a method for producing the same, a composition for screening use, and a method for selecting a cyclic peptide compound that binds to a target substance. According to the present invention, a peptide compound represented by Formula (1) or a salt thereof is provided. In the formula, the symbols have the meanings as defined in the specification of the present application.