Enhancing the gastrointestinal stability of salmon calcitonin through peptide stapling

Salmon calcitonin (sCT) is a polypeptide hormone available in the clinic. sCT is degraded in the gastrointestinal tract in minutes. In this work, a stapled analogue of salmon calcitonin, KaY-1(R24Q), was developed using the cooperative stapling between Lys and Tyr, with R24Q substitution. The analogue exhibited an improved stability in simulated gastric and intestinal fluid and retained the ability to activate the calcitonin receptor. This work will serve as a starting point for the development of an oral sCT drug.