Hectogram‐scale synthesis of [Aib8, Arg34]‐GLP‐1 (7–37) by liquid‐phase fragment condensation

• Published in: Journal of peptide science Vol. 29; no. 3; pp. e3452 - n/a
• Main Authors: Zhang, Jinhua, Zhao, Mengjia, He, Yufeng, Dong, Yuanzhen
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2023
• Subjects: [Aib8, Arg34]‐GLP‐1 (7–37); Axial compression; Compression; Condensates; DAC‐200; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Industrial production; Peptide Fragments; Purification; scale‐up synthesis; semaglutide; Synthesis; type 2 diabetes; [Aib8, Arg34]-GLP-1 (7-37); DAC-200; type 2 diabetes; scale-up synthesis; semaglutide
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.3452

Based on small‐scale synthesis (0.3 g), a 100‐g scale‐up synthesis of crude [Aib8, Arg34]‐glucagon‐like peptide‐1 (GLP‐1) (7–37) was completed. The crude [Aib8, Arg34]‐GLP‐1 (7–37) was purified using a dynamic axial compression column 200 (DAC‐200). Approximately 61 g of [Aib8, Arg34]‐GLP‐1 (7–37) with a purity of >99% was obtained through one‐step reverse‐phase chromatography. The purification yield was approximately 92%. The yield from the total reaction was approximately 60%. In summary, we developed an economical and environmentally friendly route to the synthesis and purification of crude [Aib8, Arg34]‐GLP‐1 (7–37), laying a foundation for subsequent industrial production. Large‐scale (100 g) synthesis of crude [Aib8, Arg34]‐glucagon‐like peptide‐1 (GLP‐1) (7–37) was achieved and the crude peptide was purified using a dynamic axial compression column. This economical and environmentally friendly route to [Aib8, Arg34]‐GLP‐1 (7–37) lays the foundation for subsequent industrial production.