Series Resin Reactors for Low-Solvent Peptide Synthesis
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Solution Overview
Problem
The existing Solid Phase Peptide Synthesis (SPPS) process is expensive, time-consuming, and environmentally unfriendly due to the large quantities of solvents and reagents used, leading to significant waste generation.
Innovation Solution
A system utilizing a series of reactors for coupling peptides, where de-protecting reagents and amino acids are sequentially transferred through multiple reactors, reducing the need for solvent and reagent usage by employing environmentally friendly solvents and optimizing the de-protection and coupling processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of substance
If traditional SPPS process is used with single reactor, then peptide synthesis can be performed, but large quantities of solvents and reagents are consumed leading to significant waste generation
Solution Approach 1:
The single reactor system is segmented into multiple reactors (first reactor, second reactor, third reactor) that operate in sequence. Each reactor performs a specific function (deprotection, coupling, washing) allowing reagents to be reused across multiple peptide synthesis cycles, thereby reducing overall solvent and reagent consumption while maintaining synthesis productivity
Solution Approach 2:
The patent implements a nested workflow where the output of one reactor becomes the input of the next reactor in the sequence. The deprotection reagent from the first reactor is transferred to the second reactor, and the coupling mixture from the second reactor is transferred to the third reactor, creating a nested processing chain that maximizes reagent utilization
2Loss of time
If traditional SPPS process is used, then peptide synthesis can be performed, but the process is time-consuming due to repeated de-protection and coupling steps requiring large solvent volumes
Solution Approach 1:
The patent establishes continuous useful action by implementing automated sequential transfers between reactors without interrupting the synthesis workflow. The system continuously cycles through deprotection, coupling, and washing steps across multiple reactors, eliminating idle time and reducing the total synthesis time while minimizing solvent requirements through efficient reagent reuse
3Object-affected harmful factors
If traditional SPPS process is used with protecting groups, then selective amino acid coupling can be achieved, but environmentally unfriendly solvents must be used in large quantities
Solution Approach 1:
The patent implements discarding and recovering by collecting the washing solution from the third reactor and transferring it back to the first reactor for reuse. This circular flow system recovers solvents and reagents that would otherwise be discarded, reducing the overall quantity of environmentally unfriendly solvents required while maintaining the selective coupling capability provided by protecting groups
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 significantly reduces solvent and reagent consumption, leading to a more efficient and environmentally friendly peptide synthesis process with cost savings and minimized waste production.
Implementation Method 1
adding a first quantity of de-protecting reagent to the first reactor, wherein the de-protecting reagent reacts with the protected N-group
Implementation Method 2
the activated ester from the new amino acid reacts with the newly de-protected NH2 group of the terminal amino acid, thereby coupling these two amino acids together
Data Source
AI summary
A Solid Phase Peptide Synthesis (SPPS) device and method of using the same for manufacturing peptides is taught herein. The system comprises at least two reactors, each reactor including a quantity of SPPS resin. The reactors are positioned in series. A de-protecting agent is added to the first reactor and then transferred to the second and third reactors, in series, thereby operating to de-protect the protected N-group. Wash solvent is added to the first reactor and then transferred to the second and this operation repeated several times. Likewise, an amino acid activated ester solution is added, in series, to the first, second and third reactors, thereby operating to couple the amino acid to the de-protected N-group. Wash solvent is added to the first reactor and then transferred to the second and this operation repeated several times prior to the next cycle. The use of the reactors in series reduces the overall solvent required. Online LCMS is also used to monitor progress and identity of reactions happening within the solid phase resin particles.