التفاصيل البيبلوغرافية
| العنوان: |
Recombinant Expression and Stapling of a Novel Long-Acting GLP-1R Peptide Agonist. |
| المؤلفون: |
Lear, Sam1 (AUTHOR) samlear@scripps.edu, Seo, Hyosuk1 (AUTHOR), Lee, Candy1 (AUTHOR), Lei, Lei1 (AUTHOR), Amso, Zaid1 (AUTHOR), Huang, David1 (AUTHOR), Zou, Huafei1 (AUTHOR), Zhou, Zhihong1 (AUTHOR), Nguyen-Tran, Vân T. B.1 (AUTHOR), Shen, Weijun1 (AUTHOR) wshen@scripps.edu, Pizzo, Elio (AUTHOR) |
| المصدر: |
Molecules. Jun2020, Vol. 25 Issue 11, p2508-2508. 1p. 1 Diagram, 4 Charts, 6 Graphs. |
| مصطلحات موضوعية: |
*ANIMAL models of diabetes, *GLUCAGON-like peptide-1 receptor, *METABOLIC disorders, *TYPE 2 diabetes, *POLYETHYLENE glycol, *CHEMICAL reactions |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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