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A two-step method preparation of semaglutide through solid-phase synthesis and inclusion body expression.
Peng, Dezheng; Li, Yang; Si, Linlin; Zhu, Bo; Wu, Peng; Li, Yibang; Tang, Dongfang; Liu, Yu; Zhang, Yunxiao.
Affiliation
  • Peng D; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
  • Li Y; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
  • Si L; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
  • Zhu B; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
  • Wu P; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
  • Li Y; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
  • Tang D; Department of Chemical and Biological Engineering, Hunan University of Science and Engineering, Yongzhou, 425199, Hunan, China.
  • Liu Y; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China; Shenzhen Pengtai Biotechnology Co., Ltd, Shenzhen, 518000, Guangdong, China. Electronic address: hiliu2000@126.com.
  • Zhang Y; School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China; Key Laboratory of Hunan Province for Advanced Carbon-based Functional Materials, School of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 4
Protein Expr Purif ; 219: 106477, 2024 Jul.
Article in En | MEDLINE | ID: mdl-38527576
ABSTRACT
Semaglutide is currently the most promising antidiabetic drug, especially for the treatment of type 2 diabetes mellitus, due to its excellent efficacy in glycemic control and weight loss. However, the production of semaglutide remains high cost, and high yield, low cost, and high purity still remains a challenge. Herein, we reported a convenient and high-yield strategy for the preparation of semaglutide through fragmented condensation coupling, involving solid-phase peptide synthesis of tetrapeptide and on-column refolding and on-column enzyme cleavage based inclusion body expression of Lys26Arg34GLP-1 (11-37) with fused protein tags in an X-Y-D4K-G pattern. The optimized N-terminal protein tag significantly boosts inclusion body expression level, while on-column refolding and on-column enzyme cleavage avoid precipitation, enhancing efficiency and yield together with one-step purification. The successful preparation of semaglutide is expected to achieve large-scale industrial production with low cost, high yield and high purity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Inclusion Bodies / Glucagon-Like Peptides / Solid-Phase Synthesis Techniques Limits: Humans Language: En Journal: Protein Expr Purif Journal subject: BIOLOGIA MOLECULAR Year: 2024 Type: Article Affiliation country: China
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Inclusion Bodies / Glucagon-Like Peptides / Solid-Phase Synthesis Techniques Limits: Humans Language: En Journal: Protein Expr Purif Journal subject: BIOLOGIA MOLECULAR Year: 2024 Type: Article Affiliation country: China