Analogs and Conjugates of Natural Proline-Arginine-Rich Antimicrobial Peptides: Application Potential

Abstract Antimicrobial peptides (AMPs) and, in particular, proline-arginine-rich cationic AMPs (PrAMPs) have recently attracted attention as potential candidates for developing new-generation antibacterial drugs. This interest stems from the fact that PrAMPs can target antibiotic-resistant bacteria and utilize a unique mechanism, which involves an interaction with bacterial ribosomes and inhibition of protein synthesis. Additionally, PrAMPs have a broad spectrum of activity against Gram-negative bacteria, show low rates of bacterial resistance, and are relatively easy to modify structurally. Several factors limit PrAMPs application, including their susceptibility to proteolytic degradation in biological media and their insufficiently broad spectrum of antibacterial activity against Gram-positive bacteria. Bacteria may develop PrAMP resistance, and toxic effects may result from the interactions of PrAMPs with certain components of eukaryotic cells. To overcome these challenges, it is possible to modify the PrAMP structure or create conjugates of PrAMPs with other molecules. The review summarizes the recent literature on PrAMP analogs and conjugates and considers the methods of modifying PrAMPs. New properties of compounds derived from PrAMPs highlight their potential for creating effective antibacterial agents.