RESUMEN
The development of antibiotic resistance has caused significant health problems. Antimicrobial peptides (AMPs) are considered next-generation antibiotics. Protegrin-1 (PG-1) is a ß-hairpin AMP with a membrane-binding capacity. This study used twelve PG-1 analogs with different amino acid substitutions. Coarse-grained molecular dynamics (MD) simulations were used to assess these analogs, and their physicochemical properties were computed using the Antimicrobial Peptide Database. Three AMPs, PEP-D, PEP-C, and PEP-H, were chosen and synthesized for antibacterial testing. The microbroth dilution technique and hemolytic assays evaluated the antimicrobial efficacy and cellular toxicity. The checkerboard method was used to test the combined activity of AMP and standard antibiotics. Cell membrane permeability and electron microscopy were used to evaluate the mode of action. The chemical stability of the selective AMP, PEP-D, was assessed by a validated HPLC method. PEP-D consists of 16-18 amino acid residues and has a charge of +7 and a hydrophobicity of 44 %, similar to PG-1. It can efficiently inactivate bacteria by disrupting cell membranes and significantly reducing hemolytic activity. Chemical stability studies indicated that AMP was stable at 40 °C for six months under autoclave conditions. This study could introduce the potential therapeutic application of selective AMP as an anti-infective agent.
RESUMEN
Antimicrobial peptides (AMPs), a class of antimicrobial agents, possess considerable potential to treat various microbial ailments. The broad range of activity and rare complete bacterial resistance to AMPs make them ideal candidates for commercial development. These peptides with widely varying compositions and sources share recurrent structural and functional features in mechanisms of action. Studying the mechanisms of AMP activity against bacteria may lead to the development of new antimicrobial agents that are more potent. Generally, AMPs are effective against bacteria by forming pores or disrupting membrane barriers. The important structural aspects of cytoplasmic membranes of pathogens and host cells will also be outlined to understand the selective antimicrobial actions. The antimicrobial activities of AMPs are related to multiple physicochemical properties, such as length, sequence, helicity, charge, hydrophobicity, amphipathicity, polar angle, and also self-association. These parameters are interrelated and need to be considered in combination. So, gathering the most relevant available information will help to design and choose the most effective AMPs.