Front Cover: Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin (Chem. Eur. J. 36/2019). Issue 36 (16th May 2019)

• Record Type: Journal Article
• Authors: Weil‐Ktorza, Orit; Rege, Nischay; Lansky, Shifra; Shalev, Deborah E.; Shoham, Gil; Weiss, Michael A.; Metanis, Norman
• Is Part Of: Chemistry. Volume 25:Issue 36(2019)
• Page Start: 8426
• Page End: 8426
• Publication Date: 2019-05-16
• Subjects: chemical protein synthesis -- insulin -- oxidative protein folding -- protein engineering -- protein modifications -- selenocysteine; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201901973
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract : 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. on page 8513 .