Biased agonism in peptide-GPCRs: A structural perspective

G protein-coupled receptors (GPCRs) are dynamic membrane receptors that transduce extracellular signals to the cell interior by forming a ligand–receptor-effector (ternary) complex that functions via allosterism. Peptides constitute an important class of ligands that interact with their cognate GPCRs (peptide-GPCRs) to form the ternary complex. “Biased agonism”, a therapeutically relevant phenomenon exhibited by GPCRs owing to their allosteric nature, has also been observed in peptide-GPCRs, leading to the development of selective therapeutics with fewer side effects. In this review, we have focused on the structural basis of signalling bias at peptide-GPCRs of classes A and B, and reviewed the therapeutic relevance of bias at peptide-GPCRs, with the hope of contributing to the discovery of novel biased peptide drugs.