ArticleChemical science2025
Rapid synthesis of glycosylated insulins by flow-based peptide synthesis.
Article in Chemical science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Article
- Stirring glycopeptides away from the constraints of solid-phase synthesis misconceptions.Frontiers in molecular biosciences · 2026Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin is a key life-saving drug for patients with diabetes and is used clinically worldwide. To address the physicochemical challenges of insulin, such as low solubility and aggregation, glycosylated insulins have been chemically synthesized, exhibiting improved stability due to the hydration effect of glycans. In this work, we demonstrated the rapid synthesis of glycosylated insulins (glycoinsulins) using flow-based solid-phase peptide synthesis (SPPS). The insulin A-chain and glycosylated B-chain were synthesized by flow-based SPPS, with each elongation cycle completed in just 3 minutes. Through our investigations, the glycosylation step was successfully performed within 10 minutes under optimized flow-based conditions. Additionally, we examined the incorporation of dipeptide units (isoacyl dipeptide and pseudoproline) under flow conditions and demonstrated efficient peptide elongation by combining flow-based SPPS with these dipeptide units. The synthesized A- and B-chains were subsequently used for the stepwise formation of disulfide bond linkages. The resulting glycoinsulins exhibited comparable binding affinities to insulin receptors. These findings highlight a novel flow-based approach for the rapid synthesis of glycosylated peptide and protein drugs.
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Registered trials
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