SNAC-tagged fusion peptides enable high-yield, 98% pure semaglutide P29 intermediate production.

The global burden of Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder marked by insufficient insulin secretion and impaired cellular response, necessitates effective and accessible treatments. Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, is highly effective for glycemic control and weight loss in T2DM and obesity. However, its industrial production faces significant challenges, including limited yield and high manufacturing costs, hindering wider accessibility. This study addresses the critical need for improved production efficiency and cost reduction for semaglutide intermediates.

Researchers developed a novel strategy for producing semaglutide main chain P29 (Arg34GLP-1 (9-37)), a key intermediate. The method utilized a series of semaglutide-derived helical fusion pro-peptides. These pro-peptides incorporated a specific sequence, GSHHWHHHSSGDDDDK, designed for a two-step cleavage process. The first step involved sequence-specific nickel-assisted chemical protein cleavage, followed by enterokinase cleavage. The primary endpoint was the yield and purity of the target semaglutide intermediate.

The novel production strategy demonstrated significantly improved productivity for the semaglutide P29 intermediate. The target peptide was highly expressed and purified, achieving a remarkable 98% purity. > Yields consistently exceeded 5 grams per liter of broth, representing a substantial improvement over previously reported conventional production strategies. This high-yield, high-purity outcome establishes an efficient and scalable platform for semaglutide intermediate production, addressing a major bottleneck in its manufacturing. The method leverages specific chemical and enzymatic cleavage steps to precisely isolate the desired peptide sequence from the fusion construct.