Design of Potent and Proteolytically Stable Biaryl-Stapled GLP-1R/GIPR Peptide Dual Agonists was written by Yang, Yifang;Lee, Candy;Reddy, Reddy Rajasekhar;Huang, David J.;Zhong, Weixia;Nguyen-Tran, Van T. B.;Shen, Weijun;Lin, Qing. And the article was included in ACS Chemical Biology in 2022.Application In Synthesis of 1-Bromopyrrolidine-2,5-dione This article mentions the following:
Recent clin. trials have revealed that the chimeric peptide hormones simultaneously activating glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) demonstrate superior efficacy in glycemic control and body weight reduction, better than those activating the GLP-1R alone. However, the linear peptide-based GLP-1R/GIPR dual agonists are susceptible to proteolytic cleavage by common digestive enzymes present in the gastrointestinal tract and thus not suitable for oral administration. Here, we report the design and synthesis of biaryl-stapled peptides, with and without fatty diacid attachment, that showed potent GLP-1R/GIPR dual agonist activities. Compared to a linear peptide dual agonist and semaglutide, the biaryl-stapled peptides displayed drastically improved proteolytic stability against the common digestive enzymes. Furthermore, two stapled peptides showed excellent efficacy in an oral glucose tolerance test in mice, owing to their potent receptor activity in vitro and good pharmacokinetics exposure upon s.c. injection. By exploring a more comprehensive set of biaryl staplers, we expect that this stapling method could facilitate the design of the stapled peptide-based dual agonists suitable for oral administration. In the experiment, the researchers used many compounds, for example, 1-Bromopyrrolidine-2,5-dione (cas: 128-08-5Application In Synthesis of 1-Bromopyrrolidine-2,5-dione).
1-Bromopyrrolidine-2,5-dione (cas: 128-08-5) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.Application In Synthesis of 1-Bromopyrrolidine-2,5-dione
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary