Total synthesis of human hepcidin through regioselective disulfide-bond formation by using the safety-catch cysteine protecting group 4,4'-dimethylsulfinylbenzhydryl

Dekan, Zoltan, Mobli, Mehdi, Pennington, Michael W., Fung, Eileen, Nemeth, Elizabeta and Alewood, Paul F. (2014) Total synthesis of human hepcidin through regioselective disulfide-bond formation by using the safety-catch cysteine protecting group 4,4'-dimethylsulfinylbenzhydryl. Angewandte Chemie International Edition, 53 11: 2931-2934. doi:10.1002/anie.201310103

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Author Dekan, Zoltan
Mobli, Mehdi
Pennington, Michael W.
Fung, Eileen
Nemeth, Elizabeta
Alewood, Paul F.
Title Total synthesis of human hepcidin through regioselective disulfide-bond formation by using the safety-catch cysteine protecting group 4,4'-dimethylsulfinylbenzhydryl
Formatted title
Total synthesis of human hepcidin through regioselective disulfide-bond formation by using the safety-catch cysteine protecting group 4,4′-dimethylsulfinylbenzhydryl
Journal name Angewandte Chemie International Edition   Check publisher's open access policy
ISSN 1433-7851
1521-3773
Publication date 2014-03-10
Year available 2014
Sub-type Article (original research)
DOI 10.1002/anie.201310103
Open Access Status Not yet assessed
Volume 53
Issue 11
Start page 2931
End page 2934
Total pages 4
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Language eng
Abstract 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, 1) and 4.4 nm (non-native fold, 2), with 2 undergoing isomerization to 1 in the presence of ferroportin expressing cells.
Formatted abstract
A newly developed 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, 1) and 4.4 nᴍ (non-native fold, 2), with 2 undergoing isomerization to 1 in the presence of ferroportin expressing cells.
Keyword Disulfide bonds
Hepcidin
Peptides
Protecting groups
Regioselective folding
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP1096866
FT110100925
Institutional Status UQ
Additional Notes Article first published online: 7 FEB 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
Centre for Advanced Imaging Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 20 Feb 2014, 00:44:37 EST by Sandrine Ducrot on behalf of Institute for Molecular Bioscience