Cyclized Peptide Production via Temporary S-S Bond Protection
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Solution Overview
Problem
Conventional methods for producing cyclized peptides with intramolecular S—S crosslinked structures face challenges such as low yield due to alkylation of SH groups by protecting group debris and impurities, requiring low substrate concentrations to prevent side reactions, and inefficiencies in cyclization reactions.
Innovation Solution
A method involving the formation of temporary S—S bonds in peptides with two or more SH groups, followed by a folding step under oxidation and reduction conditions to re-form S—S bonds, allowing for efficient production of cyclized peptides even at higher concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If all protective groups are removed using acids such as TFA to deprotect SH groups, then the SH groups become available for cyclization, but the debris from protective groups causes alkylation of SH groups and decreases yield
Solution Approach 1:
The patent applies preliminary action by forming temporary S-S bonds to protect SH groups before the cyclization reaction. This protective measure is taken in advance to prevent alkylation by protecting group debris, thereby maintaining high cyclization yield without requiring complete removal of all protective groups.
2Reliability
If substrate concentration is kept low to suppress intermolecular side reactions, then cyclization can proceed, but production efficiency decreases due to excessive solvent use
Solution Approach 1:
The patent uses temporary S-S bonds as intermediaries to protect SH groups during the cyclization reaction. This intermediary protection allows the reaction to proceed at higher substrate concentrations without unwanted intermolecular side reactions, thereby improving production efficiency while maintaining selectivity.
3Reliability
If multiple combinations of S-S bond formation are possible in peptides with 4 or more SH groups, then cyclization can occur, but selective formation of desired S-S bonds becomes difficult
Solution Approach 1:
The patent applies preliminary action by forming temporary S-S bonds in a controlled manner before the final cyclization. This preliminary structuring guides the subsequent oxidative folding to form the desired S-S bond combinations selectively, even in peptides with multiple SH groups, thereby simplifying the overall process complexity.
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
This approach enhances the yield and efficiency of cyclization reactions by protecting SH groups with temporary S—S bonds, reducing the impact of impurities and enabling higher concentration processing, thus overcoming the limitations of traditional methods.
Implementation Method 1
a cyclization reaction by which a cyclized peptide is obtained by forming an intramolecular S—S bond
Implementation Method 2
subjecting the peptide obtained in step (1) to a folding step under oxidation and reduction conditions
Data Source
AI summary
Cyclized peptides having a crosslinked structure by one or more intramolecular S—S bonds may be prepared by:(1-A) as to a completely protected linear peptide having two or more SH groups as functional groups on the peptide, removing protecting groups of all functional groups other than the protected SH groups in the peptide,(1-B) protecting all SH groups of the linear peptide having two or more SH groups as the functional groups on the peptide by forming a temporary S—S bond,and(2) subjecting the peptide obtained by step (1-A) and step (1-B) to a folding step under oxidation and reduction conditions to obtain the cyclized peptide by re-forming an S—S bond in the peptide molecule.