5 years ago

Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin

Orit Weil‐Ktorza, Nischay Rege, Shifra Lansky, Deborah E. Shalev, Gil Shoham, Michael A. Weiss, Norman Metanis
Chemical preparation of insulin is challenging due to the two‐chain (designated A and B) structure of this hormone, which exhibits a specific pattern of disulfide pairing. Traditional methods of synthesis, based on chain combination, are limited by slow and inefficient disulfide pairing. This limitation can be overcome by use of a modified A chain, in which cysteine residues at positions 6 and 11 are replaced with selenocysteines. The product seleno‐insulin (containing an internal A6–A11 diselenide bond) was rapidly obtained in high yield. The analogue retains native binding to the insulin receptor and exhibits augmented stability. More information can be found in the Full Paper by M. A. Weiss, N. Metanis et al. (DOI: 10.1002/chem.201900892).
Open access
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