Progress in regulatory peptide research

Abstract

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 proteincoupled 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.

Studies of cell-penetrating peptides by biophysical methods

“…In this respect, they were intensively studied, in the last years, particularly for introducing anticancer molecules into tumors (Zorko et al ., 2022). Dozens of peptide-based drugs have been approved for clinical use (Zhang and Eiden, 2019), but among them, CPPs could not be found. Although CPPs have been known for more than 30 years, they have not yet entered clinical practice.…”

Prediction and Analysis of Key Protein Structures of 2019-nCoV

“…The structures of these proteins are common targets for drug development. Taking the PLpro structure obtained by homology modeling as a target, and using a peptide with low toxicity and favorable for clinical acceleration as an example [22], the full-sequence library of tripeptides was subjected to screening of antivitual drugs. Finally, the tripeptide with amino acid sequence Val-Val-Asn (TP8) with strong binding ability to ACE2 was obtained.…”

A peptide encoded by pri‐miRNA‐31 represses autoimmunity by promoting T reg differentiation

“…Peptide drugs display unparalleled advantages, such as ready synthesis, quick optimization, fewer immune responses, fewer toxic side effects, and rapid clearance (Fosgerau & Hoffmann, 2015). Dozens of peptide-based drugs have been approved by the U.S. Food and Drug Administration (FDA) over the past decade, the majority for the treatment of metabolic disorders, including diabetes, with many more under clinical and preclinical studies, among which insulin is the most popular (Kaspar & Reichert, 2013;Zhang & Eiden, 2019). Compared with small molecule drugs, the time required for peptides to move from clinical trials to FDA approval is much shorter, and peptides are two times more likely to pass clinical trials (de la Torre & Albericio, 2018).…”