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Three‐chain insulin analogs demonstrate the importance of insulin secondary structure to bioactivity
Author(s) -
Wu Fangzhou,
Chabenne Joseph R.,
Gelfanov Vasily M.,
Mayer John P.,
DiMarchi Richard D.
Publication year - 2015
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2744
Subject(s) - insulin , insulin receptor , biological activity , peptide , chemistry , in vitro , biochemistry , human insulin , insulin receptor substrate , biology , insulin resistance , endocrinology
This report describes the chemical synthesis and biological characterization of novel three‐chain insulin analogs with a destabilized secondary structure. The analogs, obtained by chemical synthesis via a single‐chain precursor and selective enzymatic digestion, were used to investigate the role of the highly conserved ‘insulin fold’. Biological characterization through in vitro biochemical signaling showed extremely low activity at each insulin receptor when compared with native insulin. We conclude that the ‘insulin fold’ is a structural foundation that supports insulin biological action. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.