ABSTRACT
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in mammals that contain seven transmembrane helices. The human genome encodes about 800 different types of GPCRs, which are widely involved in the pathological processes underlying different diseases, e.g. metabolic diseases and tumors, rendering them popular therapeutic targets. Peptides are organic substances consisted of two to dozens of amino acids linked by peptide bonds. They are bioactive substances involved in various cellular activities. To date, over 7 000 natural peptides have been identified as hormones, neurotransmitters, growth factors, ion channel ligands and antibiotics. Peptide drugs are valued for being selective and efficacious, and at the same time relatively safe and with low costs of production. In recent years, based on the increased understanding of GPCR structures, the development of GPCR-targeting peptide drugs has made great progress. Up to now, there have been nearly 50 peptide drugs targeting GPCRs approved by FDA for the treatment of metabolic diseases, nervous system diseases, cancer or other diseases. The research and development of peptide drugs have gone through three stages: development based on human peptides, on natural peptides and by modern biotechnology. At present, most of the marketed GPCR-targeting peptide drugs are derivatives of human natural peptides. In this review, we sum up the recent marketed GPCR-targeting peptide drugs, and also summarize the current strategies and further directions of peptide drug development.