Peptide Linker Purification on Reusable Solid Phase Supports
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Solution Overview
Problem
Existing methods for peptide purification, such as preparative HPLC, are costly, not scalable, and unsuitable for sulfur-containing or copper-binding peptides, and require complex equipment and solvents, while solid phase methods face issues with reuse and stability of solid phases and peptides.
Innovation Solution
A method using linker molecules that immobilize peptide precursors for purification and modification on a solid support, allowing simultaneous purification and modification, suitable for sulfur-containing peptides, and enabling reuse of the solid phase.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If HPLC is used for peptide purification, then purification quality is improved, but production cost increases and scalability decreases
Solution Approach 1:
The patent introduces a linker molecule as an intermediary that covalently connects the peptide to a solid phase support. This mediator enables the peptide to be immobilized during purification, allowing for simplified purification methods that are more scalable and cost-effective while maintaining purification quality. The linker acts as a bridge between the peptide and the solid phase, facilitating the purification process without requiring complex HPLC systems.
2Manufacturing precision
If traditional solid phase methods are used, then purification is achieved, but the solid phase cannot be reused and costs increase
Solution Approach 1:
The patent implements a system where the solid phase support is recovered and reused after purification. The linker molecule is designed to allow the peptide to be cleaved from the solid phase while the solid phase itself remains intact and can be regenerated for subsequent purification cycles. This recovering aspect eliminates the need to discard the expensive solid phase after single use, significantly reducing production costs while maintaining purification effectiveness.
3Manufacturing precision
If sulfur-containing peptides are purified using traditional methods, then purification is attempted, but copper complexation occurs making copper removal difficult and the method inapplicable
Solution Approach 1:
The patent extracts or removes copper from the purification system entirely. By using a solid phase support with specific functional groups that do not require copper for the purification mechanism, the method eliminates copper complexation with sulfur-containing peptides. The linker and solid phase are designed to achieve purification through alternative mechanisms that are compatible with sulfur-containing amino acids, thereby removing the harmful copper toxicity issue while maintaining purification capability.
4Ease of manufacture
If linear peptides are used, then synthesis is simple, but in vivo stability is low due to fast degradation
Solution Approach 1:
The patent applies preliminary action by performing cyclization of the peptide during the solid phase synthesis process itself, before the peptide is cleaved from the solid phase. The linker molecule facilitates this in-situ cyclization, creating cyclic peptides that have enhanced in vivo stability against proteolytic degradation. This preliminary cyclization step maintains synthesis simplicity while dramatically improving the stability of the final peptide product.
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 reduces costs and complexity by eliminating the need for HPLC systems, supports scalable production, and allows for efficient purification and reuse of solid phases, while maintaining peptide stability and functionality.
Implementation Method 1
reversible hydrazone or oxime bonds
Implementation Method 2
reversible hydrazone or oxime bonds
Implementation Method 3
covalently bound to the N-terminal end of the synthesized full-length peptide
Data Source
AI summary
The present invention relates to a method for the purification of peptides which are produced by solid phase peptide synthesis (SPPS) and corresponding linker molecules for use in said method. Optionally, the peptide may be modified while bound via said linker molecule on a purification support.