Year: 2018
Type: article
Abstract: Significance G-protein-coupled receptors (GPCRs) mediate diverse physiological processes and are targets of many therapeutic agents. GPCR subfamilies comprise related receptors that can be activated by the same or similar agonists but manifest distinct functions. Subtype-selective agonists are valuable as tools for fundamental research and as drug candidates with minimal side effects. It is challenging, however, to develop agonists with differentiated activities at structurally related receptors. We started from a human parathyroid hormone fragment that is used to treat osteoporosis, and developed subtype-selective variants by modifying the peptide backbone while maintaining the natural side chains. Our findings suggest that backbone modification, which has received little prior attention in terms of tailoring polypeptide hormone specificity, may represent a general source of receptor-selective agonists.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2901348230