J Pept Sci 2015 Mar 9;21(3):223-30. Epub 2015 Feb 9.
Department of Chemistry, Indiana University, Bloomington, IN, 47405, USA.
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.