Recombinant Expression and Stapling of a Novel Long-Acting GLP-1R Peptide Agonist.
Molecules
; 25(11)2020 May 28.
Article
em En
| MEDLINE
| ID: mdl-32481528
ABSTRACT
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 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 staple in a subsequent chemical reaction step.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor do Peptídeo Semelhante ao Glucagon 1
/
Exenatida
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article