Aqueous Solid-Phase Peptide Synthesis with Resin Swelling Control
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Solution Overview
Problem
Existing solid-phase peptide synthesis (SPPS) methods rely heavily on organic solvents that are hazardous to human health and require excessive use of reactants, leading to significant waste and environmental concerns, while also being inefficient in solubilizing Fmoc-protected amino acids and maintaining resin swelling for optimal peptide bond formation.
Innovation Solution
The method employs an aqueous solution with an organic co-solvent miscible with water to solubilize Fmoc-protected amino acids and uses a resin that swells at least 4 mL/g, allowing for peptide bond formation under thermodynamically favorable conditions, reducing the need for excess reactants and enabling solvent regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If organic solvents are used in SPPS to solubilize Fmoc-protected amino acids, then solubility is improved, but harmful factors and environmental impact increase
Solution Approach 1:
The invention changes the solvent composition parameters by using an aqueous solution with a specific co-solvent (ethyl acetate or isopropyl alcohol) at controlled concentrations (5-50% v/v), transforming the traditional organic solvent system into a safer aqueous-based system that maintains solubility while reducing harmful effects
Solution Approach 2:
The invention employs commonly available, low-toxicity solvents (water, ethyl acetate, isopropyl alcohol) that are safer for human health and environment, replacing hazardous organic solvents while maintaining effectiveness in solubilizing Fmoc-protected amino acids
2Productivity
If excess reactants are used to drive peptide bond formation, then reaction yield is improved, but waste and loss of substance increase
Solution Approach 1:
The invention changes the reaction conditions by using an aqueous co-solvent system that improves the thermodynamics of peptide bond formation, allowing the reaction to proceed efficiently with near-stoichiometric amounts of reactants, thereby reducing waste while maintaining high yield
Solution Approach 2:
The aqueous co-solvent acts as an intermediary that facilitates peptide bond formation by improving solubility and reaction thermodynamics, enabling the reaction to proceed efficiently without requiring large excesses of reactants
3Productivity
If traditional organic solvents are used in SPPS, then peptide synthesis can proceed, but resin swelling is insufficient for optimal reaction
Solution Approach 1:
The invention changes the solvent parameters by introducing an aqueous co-solvent system that specifically enhances resin swelling capacity, increasing the volume available for reaction while maintaining peptide synthesis efficiency
4Quantity of substance
If Fmoc-protected amino acids are used in traditional organic solvents, then solubility is adequate, but human health and environment are harmed
Solution Approach 1:
The invention changes the solvent system parameters by using an aqueous base with controlled amounts of safe co-solvents (ethyl acetate or isopropyl alcohol), reducing the harmful environmental impact while maintaining adequate solubility of Fmoc-protected amino acids
Solution Approach 2:
The invention replaces hazardous organic solvents with safer, commonly available alternatives (water, ethyl acetate, isopropyl alcohol) that have lower environmental impact and are safer for human health, while maintaining solubility effectiveness
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 minimizes the use of harmful organic solvents, enhances solubility and resin swelling, and maintains high yield in peptide synthesis, while facilitating solvent recycling and reducing environmental impact.
Implementation Method 1
The aqueous solution comprising a co-solvent is capable of solubilizing appropriately activated Fmoc-protected amino acids and peptide fragments
Implementation Method 2
the base resin has the characteristic to swell at least 4 mLg−1 in the aqueous solution
Implementation Method 3
The amide bonds are typically formed by a condensation reaction of a carboxyl group of one amino acid with the amino groups of another amino acid
Data Source
AI summary
The present invention relates to a solid phase peptide synthesis (SPPS) where the coupling of amino acids is performed in an aqueous solution comprising at least one organic co-solvent miscible with water. The aqueous solution is capable of sufficiently solubilize the activated Fmoc-α-amine protected amino acid or activated Fmoc-α-amine protected peptide fragment, and where the resin is capable of swelling in the presence of the aqueous solution above about 4 mLg−1. The invention also encompasses a method for regeneration of spent aqueous solution from the SPPS.