Enhancing the gastrointestinal stability of salmon calcitonin through peptide stapling

Hiba Ghareeb; Norman Metanis

doi:10.1039/d3cc01140b

Enhancing the gastrointestinal stability of salmon calcitonin through peptide stapling

Chem Commun (Camb). 2023 May 30;59(44):6682-6685. doi: 10.1039/d3cc01140b.

Authors

Hiba Ghareeb¹, Norman Metanis^{1

2

3}

Affiliations

¹ Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel. metanis@mail.huji.ac.il.
² Casali Center for Applied Chemistry, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
³ The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.

PMID: 37186112
DOI: 10.1039/d3cc01140b

Abstract

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.

MeSH terms

Animals
Calcitonin*
Gastrointestinal Tract
Peptides*
Salmon

Substances

salmon calcitonin
Calcitonin
Peptides