Progress in regulatory peptide research.

The field of regulatory peptide research has developed significant momentum owing to several recent converging trends. Dozens of peptide-based drugs have been approved by the U.S. Food and Drug Administration in the past decade, the majority for the treatment of metabolic disorders, including diabetes. These are the "tip of the spear" for peptide therapeutics, revealing that impediments of delivery, stability, and bioavailability inherent in peptide drugs have in many cases been overcome. While most are orally available, and directed at peripheral targets, pharmaceutical delivery of peptides to the central nervous system through nasal mucosal routes has also seen much progress. Cell-based high-throughput drug discovery methods, the X-ray crystallographic structural definition of G protein-coupled receptors, and deorphanization of peptide-liganded receptors have contributed to the emergence of new targets for pharmacological intervention and accelerated the development of peptide-based as well as nonpeptide congeners for existing ones. Finally, the recognition that peptides act at their receptors, in a cellular context, in conjunction with other peptides and other first messengers, including neurotransmitters, hormones, and autocrine and paracrine factors, has led to an increased appreciation for the combinatorial possibilities of regulatory peptide action, now penetrating to drug design and discovery efforts. The fifteen reviews, reports, and perspectives collected in this special issue of Annals of the New York Academy of Sciences provide a snapshot of the frontiers of the field of regulatory peptide research as they expand physiologically, pharmacologically, and therapeutically.