Jul 25, 2023

Computational Design of Potent and Selective d-Peptide Agonists of the Glucagon-like Peptide-2 Receptor

Journal of medicinal chemistry
Pedro A Valiente, Satra Nim, Jisun Kim, Philip M Kim
Here, we designed three d-GLP-2 agonists that activated the glucagon-like peptide-2 receptor (GLP-2R) cyclic adenosine monophosphate (cAMP) accumulation without stimulating the glucagon-like peptide-1 receptor (GLP-1R). All the d-GLP-2 agonists increased the protein kinase B phosphorylated (p-AKT) expression levels in a time- and concentration-dependent manner in vitro. The most effective d-GLP-2 analogue boosted the AKT phosphorylation 2.28 times more effectively compared to the native l-GLP-2....