Peptide Synthesis via One-Pot Precipitation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional peptide synthesis methods using the anchor method require multiple isolation and purification steps, leading to increased time and cost, and the risk of undesirable side reactions due to residual amino acids, which hinders industrialization.
Innovation Solution
A method that omits intermediate isolation and purification by using a temporary protecting group for the N-terminal amino group, allowing for successive one-pot operations through condensation and deprotection steps, with precipitation and solid-liquid separation using a water-acetonitrile mixture to remove residual amino acids effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If multiple isolation and purification steps are performed in conventional anchor method, then purity of peptide is improved, but time and cost increase significantly
Solution Approach 1:
The patent combines multiple isolation and purification steps into a single precipitation operation. By using a specific solvent system (acetonitrile-water mixture) and controlling precipitation conditions, the method achieves both concentration and purification in one step, eliminating the need for separate filtration, washing, and drying operations that would otherwise be required.
Solution Approach 2:
The patent changes the solvent composition parameter by using a specific acetonitrile-water mixture ratio (60:40 to 95:5 v/v) to achieve optimal precipitation. This parameter optimization allows for efficient solid-liquid separation while maintaining high peptide purity, reducing the number of operational steps required.
2Manufacturing precision
If multiple isolation and purification steps are performed, then peptide purity is improved, but operational complexity increases
Solution Approach 1:
The patent merges concentration, precipitation, filtration, washing, and drying into a single integrated precipitation operation. This consolidation reduces operational complexity by eliminating multiple discrete steps while maintaining peptide purity through controlled precipitation conditions.
Solution Approach 2:
The patent employs a self-service approach where the peptide product automatically separates from impurities through precipitation in the acetonitrile-water mixture. The solid-liquid separation occurs naturally based on solubility differences, reducing the need for complex external purification mechanisms.
3Reliability
If intermediate isolation is performed, then side reactions are prevented, but productivity decreases
Solution Approach 1:
The patent extracts residual amino acids and impurities from the reaction mixture through selective precipitation. By using the acetonitrile-water solvent system, impurities are separated from the desired peptide product, preventing side reactions in subsequent steps while maintaining high synthesis efficiency through continuous processing.
Solution Approach 2:
The acetonitrile-water mixture acts as an intermediary solvent system that facilitates both reaction progression and impurity removal. This mediator enables the peptide synthesis to proceed efficiently while simultaneously preparing the product for purification through controlled precipitation.
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 enables high-yield, high-purity peptide production with reduced operational complexity, making it suitable for industrial-scale synthesis by minimizing side reactions and simplifying the process.
Implementation Method 1
precipitating the peptide in a solvent containing water-containing acetonitrile after removing the N-terminal temporary protecting group
Implementation Method 2
obtaining the peptide by solid-liquid separation
Data Source
AI summary
The present invention provides a production method of a protected amino acid, protected peptide or peptide, including precipitation and solid-liquid separation of C-protected amino acid or C-protected peptide in a solvent containing water-containing acetonitrile, after removing the N-terminal protecting group from N-protected C-protected amino acid or N-protected C-protected peptide wherein the C-terminal carboxy group is protected by an anchor group.