Oligopeptides as molecular carriers in antimicrobial conjugates

One of the reasons for the decreasing effectiveness of modern antimicrobial chemotherapy and the increasing resistance of pathogenic microorganisms to drugs is a hampered access of active agents to intracellular targets, due to the problems with crossing the biological membrane barriers.

This article discusses the possibilities and methods of using oligopeptides that penetrate cell membranes by simple diffusion, endocytosis, or using active transport systems, as molecular carriers for the construction of antimicrobial conjugates, following the Trojan Horse strategy. The basis for the discussion and conclusions is a critical review of the literature from 1970 to 2025, searched in Web of Science, PubMed, and Scopus, with a strong emphasis on examples from the last decade.

Application of short peptides transported by microbial oligopeptide transport systems, cell penetrating peptides, and antimicrobial peptides as molecular carriers may give rise to novel antimicrobial conjugates, able to overcome microbial resistance, as well as to enhancement of antimicrobial potential and broadening of antimicrobial spectrum of existing drugs, especially against intracellular microbial pathogens.