O-GlcNAc Engineering of GPCR Peptide-Agonists Improves Their Stability and in Vivo Activity.

ABSTRACT: Peptide agonists of GPCRs and other receptors are powerful signaling molecules with high potential as biological tools and therapeutics, but they are typically plagued by instability and short half-lives in vivo. Nature uses protein glycosylation to increase the serum stability of secreted proteins. However, these extracellular modifications are complex and heterogeneous in structure, making them an impractical solution. In contrast, intracellular proteins are subjected to a simple version of glycosylation termed O-GlcNAc modification. In our studies of this modification, we found that O-GlcNAcylation inhibits proteolysis, and strikingly, this stabilization occurs despite large distances in primary sequence (10-15 amino acids) between the O-GlcNAc and the site of cleavage. We therefore hyp

SUBMITTER: Levine PM 

PROVIDER: S-EPMC6860926 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature