Peptide Synthesis Carrier Solubility Switch
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Solution Overview
Problem
Peptide synthesis methods face challenges in accurately elongating peptide chains, particularly with the issue of amino acid residue deletion and double hits during de-protection reactions, which affect yield and quality, especially when using carriers that reversibly change states between dissolved and insolubilized forms.
Innovation Solution
A peptide synthesis method involving the use of a carrier that changes solubility in response to solvent composition, allowing for selective separation of amino acids, where an N-Fmoc protected peptide is condensed with a C-carrier protected peptide, followed by de-protection and crystallization to prevent amino acid residue deletion and double hits, using specific amines and solvents to manage active species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If a carrier that reversibly changes between dissolved and insolubilized states is used for peptide synthesis, then separation and purification become easier, but amino acid residue deletion and double hits occur during de-protection reactions
Solution Approach 1:
The patent applies preliminary action by adding a scavenger substance before the de-protection reaction to pre-remove active species from the reaction system. This prevents the harmful effects of active species during subsequent de-protection and crystallization steps, thereby eliminating amino acid residue deletion and double hits while maintaining the benefits of carrier-based synthesis
2Device complexity
If amino acid active species are not removed before de-protection, then the synthesis process is simpler, but double hits occur during de-protection reaction
Solution Approach 1:
The patent introduces a scavenger substance as an intermediary component that mediates between the active species and the de-protection reaction. The scavenger selectively binds and removes active species without interfering with the main peptide synthesis process, thus preventing double hits while adding minimal complexity to the overall process
3Productivity
If conventional liquid phase peptide synthesis is used for large scale production, then production volume increases, but peptide elongation becomes difficult as chain length increases
Solution Approach 1:
The patent applies parameter changes by utilizing the solubility characteristics of the carrier molecule. The carrier reversibly changes between dissolved and insolubilized states, allowing peptides to be synthesized in solution and then precipitated in high purity form. This enables large-scale production while maintaining high elongation success rates even for long peptide chains
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 method effectively prevents amino acid residue deletion and double hits, resulting in high-quality peptide synthesis with improved yield by managing active species and selective separation, enhancing the versatility and efficiency of peptide elongation reactions.
Implementation Method 1
a carrier molecule which sensitively detects a change of the solvent composition thereby causing a reversible change between the dissolved state and the insolubilized (crystallized) state
Implementation Method 2
causes selective dissolution of a specific component dissolved into a specific phase at high concentration (selective distribution) in liquid phase separation
Implementation Method 3
the solidified (crystallized) substance can be easily separated and purified
Data Source
AI summary
The present invention has an object of providing a peptide synthesis method using a carrier capable of reversibly repeating the dissolved state and the insolubilized state, wherein the problem of an amino acid active species existing in the reaction system in de-protection reaction can be easily solved. The present invention provides a peptide synthesis method comprising the following steps: a step of condensing an N-Fmoc protected amino acid with a peptide having a C-terminal protected with a carrier which is crystallized according to a change of a composition of a dissolving solvent, in the presence of a condensing agent, to obtain an N-Fmoc-C-carrier protected peptide, a step of adding an alkylamine having 1 to 14 carbon atoms or hydroxyl amine to the reaction system, a step of de-protecting the N-terminal, and a step of changing the composition of the solvent dissolving the C-carrier protected peptide, to crystallize and separate the peptide.