Total Synthesis of Human Hepcidin through Regioselective Disulfide‐Bond Formation by using the Safety‐Catch Cysteine Protecting Group 4, 4′‐Dimethylsulfinylbenzhydryl1. Issue 11 (7th February 2014)

• Record Type: Journal Article
• Authors: Dekan, Zoltan; Mobli, Mehdi; Pennington, Michael W.; Fung, Eileen; Nemeth, Elizabeta; Alewood, Paul F.
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 11(2014)
• Page Start: 2931
• Page End: 2934
• Publication Date: 2014-02-07
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201310103
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A safety‐catch cysteine protecting group, S‐4, 4′‐dimethylsulfinylbenzhydryl (Msbh), was designed and developed to expand the capabilities of synthetic strategies for the regioselective formation of disulfide bonds in cysteine‐rich peptides. The directed regioselective synthesis of human hepcidin, which contains four disulfide bonds, was undertaken and led to a high‐resolution NMR structure under more physiologically relevant conditions than previously. Conversely, hepcidin synthesized with the formerly assigned vicinal disulfide‐bond connectivity displayed significant conformational heterogeneity under similar conditions. The two synthetic forms of human hepcidin induced ferroportin internalization with apparent EC₅₀ values of 2.0 (native fold, <bold>1</bold>) and 4.4 n<sc>M</sc> (non‐native fold, <bold>2</bold>), with <bold>2</bold> undergoing isomerization to <bold>1</bold> in the presence of ferroportin expressing cells.</p> </abstract>