Glycosylation Improves the Proteolytic Stability of Exenatide

Bioconjug Chem. 2023 Jun 21;34(6):1014-1018. doi: 10.1021/acs.bioconjchem.3c00120. Epub 2023 May 16.

Abstract

Exenatide was the first marketed GLP-1 receptor agonist for the treatment of type 2 diabetes. Modification to the chemical structure or the formulation has the potential to increase the stability of exenatide. We introduced human complex-type sialyloligosaccharide to exenatide at the native Asn28 position. The synthesis was achieved using both solid phase peptide synthesis (SPPS) and Omniligase-1-mediated chemoenzymatic ligation. The results demonstrate that glycosylation increases the proteolytic stability of exenatide while retaining its full biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glycosylation
  • Humans
  • Hypoglycemic Agents
  • Peptide Hydrolases
  • Venoms

Substances

  • Exenatide
  • Hypoglycemic Agents
  • Peptide Hydrolases
  • Glucagon-Like Peptide-1 Receptor
  • Venoms