LA JOLLA, Calif., March 28, 2016 /PRNewswire-USNewswire/ -- A team of researchers at the California Institute for Biomedical Research (Calibr) and The Scripps Research Institute (TSRI) have developed a peptide engineering platform to improve the effectiveness of peptide hormones as treatments for chronic diseases such as diabetes and obesity. As a drug class, peptides offer exquisite specificity and potency, but also present challenges associated with poor stability and short half-life, manifesting in the need for frequent injections, poor patient compliance, and overall compromised efficacy. The results, published today in the Proceedings of the National Academy of Sciences (PNAS) titled "Long-acting Potent GLP-1 Analog Delivered in Microstructure-based Transdermal Patch", described the development of a novel strategy that incorporates a serum protein-binding motif into a covalent side-chain "staple", which rigidifies the bioactive portion of the peptide leading to increased stability and potency.
As a proof-of-concept, this strategy has been successfully applied to generate a highly potent, long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist for the treatment of type 2 diabetes and obesity. Researchers demonstrated that their new GLP-1R agonist, E6, has significantly improved half-life and glucose tolerance following an oral glucose challenge in rodents. Chronic treatment using E6 significantly decreased body weight and fasting blood glucose, improved lipid metabolism, and also reduced hepatic steatosis in diet-induced obese (DIO) mice.