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Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
Published on: May 15, 2012
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A two-step method preparation of semaglutide through solid-phase synthesis and inclusion body expression
Dezheng Peng1, Yang Li1, Linlin Si1
1School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
Protein Expression and Purification
|March 25, 2024
Summary
A new method simplifies semaglutide production for type 2 diabetes treatment. This approach achieves high yield and purity, potentially lowering costs for this important antidiabetic drug.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Drug Development
Background:
- Semaglutide is a highly effective antidiabetic drug for type 2 diabetes mellitus, known for glycemic control and weight loss.
- Current production methods for semaglutide are costly, posing challenges for high-yield, low-cost, and high-purity manufacturing.
Purpose of the Study:
- To develop a convenient and high-yield strategy for semaglutide preparation.
- To address the challenges of cost, yield, and purity in semaglutide production.
Main Methods:
- Fragmented condensation coupling strategy.
- Solid-phase peptide synthesis of a tetrapeptide.
- On-column refolding and enzyme cleavage of Lys26Arg34GLP-1 (11-37) with fused protein tags (X-Y-D4K-G pattern).
- Optimized N-terminal protein tag for enhanced inclusion body expression.
Main Results:
- Significantly boosted inclusion body expression levels.
- On-column refolding and enzyme cleavage minimized precipitation, improving efficiency and yield.
- Achieved high purity through a one-step purification process.
Conclusions:
- The developed strategy offers a convenient and high-yield method for semaglutide preparation.
- This approach is expected to enable large-scale industrial production of semaglutide with reduced cost, high yield, and high purity.
- The findings contribute to making semaglutide more accessible for type 2 diabetes treatment.
