Recombinant Expression and Stapling of a Novel Long-Acting GLP-1R Peptide Agonist

Recombinant Expression and Stapling of a Novel Long-Acting GLP-1R Peptide Agonist

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Owing to their pleiotropic metabolic benefits, glucagon-like peptide-1 receptor (GLP-1R) agonists have been successfully utilized for treating metabolic diseases, such as type 2 diabetes and obesity.As part of our efforts in developing long-acting peptide therapeutics, we have previously reported a peptide engineering strategy that combines peptide side chain stapling with covalent merrick backcountry wet cat food integration of a serum protein-binding motif in a single step.Herein, we have used this strategy to develop a second generation extendin-4 analog rigidified with a symmetrical staple, which exhibits an excellent in vivo efficacy in an animal model of diabetes and obesity.

To simplify the scale-up manufacturing of the lead GLP-1R agonist, a semisynthesis protocol was successfully developed, which involves recombinant expression of the linear peptide followed by attachment of a polyethylene glycol (PEG)-fatty acid roneverhart.com staple in a subsequent chemical reaction step.