Therapeutic peptides: chemical strategies fortify peptides for enhanced disease treatment efficacy

Abstract

Therapeutic peptides, as a unique form of medication composed of orderly arranged sequences of amino acids, are valued for their high affinity, specificity, low immunogenicity, and economical production costs. Currently, more than 100 peptides have already secured market approval. Over 150 are actively undergoing clinical trials, while an additional 400–600 are in the preclinical research stage. Despite this, their clinical application is limited by factors such as salt sensitivity, brief residence in the bloodstream, inadequate cellular uptake, and high structural flexibility. By employing suitable chemical methods to modify peptides, it is possible to regulate important physicochemical factors such as charge, hydrophobicity, conformation, amphiphilicity, and sequence that affect the physicochemical properties and biological activity of peptides. This can overcome the inherent deficiencies of peptides, enhance their pharmacokinetic properties and biological activity, and promote continuous progress in the field of research. A diverse array of modified peptides is currently being developed and investigated across numerous therapeutic fields. Drawing on the latest research, this review encapsulates the essential physicochemical factors and significant chemical modification strategies that influence the properties and biological activity of peptides as pharmaceuticals. It also assesses how physicochemical factors affect the application of peptide drugs in disease treatment and the effectiveness of chemical strategies in disease therapy. Concurrently, this review discusses the prospective advancements in therapeutic peptide development, with the goal of offering guidance for designing and optimizing therapeutic peptides and to delve deeper into the therapeutic potential of peptides for disease intervention.