A mild and sustainable platform for disulfide bond formation in peptide manufacturing using dehydroascorbic acid

Disulfide bond formation is a key step in the manufacture of cysteine‑containing peptides, yet established oxidation methods frequently rely on hazardous reagents such as iodine or hydrogen peroxide. These approaches can introduce safety concerns, material compatibility issues, limited scalability, and undesired side reactions including over‑oxidation and oligomer formation.

We describe a new oxidation platform based on dehydroascorbic acid (DHA), the oxidized form of vitamin C, as a mild, selective, and sustainable reagent for disulfide bond formation. The method supports efficient oxidation under aqueous conditions and is compatible with both high‑concentration in‑solution processing and an integrated on‑column implementation during preparative HPLC purification. DHA‑mediated oxidation shows a consistently favorable impurity profile and avoids common side reactions observed with conventional oxidants, even for peptides with limited solubility or high aggregation propensity.

The DHA‑based platform simplifies process design by enabling higher working concentrations, reducing unit operations, and allowing oxidation to be integrated into existing purification workflows. The use of a non‑hazardous, vitamin‑derived reagent improves operational safety and equipment compatibility while significantly lowering process mass intensity and solvent consumption. Together, these features support robust scale‑up and align peptide manufacturing with modern sustainability expectations, making the technology well suited for both late‑stage development and commercial production.

About the speaker

Alexander Kleinsmann
Director R&D

Alexander Kleinsmann is an organic chemist by training and focuses on technology and process development for peptide manufacturing at Bachem’s Swiss site. He earned his PhD in the group of Prof. Boris Nachtsheim at the University of Tübingen, working on cyclic dipeptides and peptide‑based supramolecular systems. Since joining Bachem in 2015, he has contributed to the development of scalable, robust, and sustainable platforms for peptide synthesis and purification used in late‑stage development and commercial production. As Director of R&D VI, he works with cross‑functional teams on process development and characterization for large‑scale peptide manufacturing, including the evaluation and implementation of advanced technologies such as MCSGP for downstream processing