Design and Synthesis of New Cationic Antimicrobial Peptides with Low Cytotoxicity

Abstract

According to the mechanisms of antimicrobial peptides presented in current research literatures, four cationic peptides rich in arginine residues were designed and synthesized in this study. Their antimicrobial activity to four microorganisms and cytotoxicity to human dermal fibroblasts (HDFs) were evaluated. Among these peptides, PEP-1, PEP-2 and PEP-4 could inhibit and kill these microorganisms at certain concentrations. While PEP-3 only exhibited low inhibition activity against E. coli. PEP-1 rich in arginine residues was more effective against Gram-negative bacteria. PEP-4 with tryptophan and lysine residues in the sequence exhibited enhancement in the antimicrobial activity compared with PEP-3 and presented lowest minimal bactericidal concentration (MBC) to S. aureus and C. albicans in these four peptides. These results indicate that the amount and position of cationic residues in the sequence affects the bactericidal activity and the complement of proline with arginine, tryptophan with arginine and lysine residues would enhance the antimicrobial activity. Moreover, PEP-1, PEP-2 and PEP-4 showed low toxicity at their 1× MBC with no considerable difference with the negative control group in the HDFs cytotoxicity test. This study provides us with a better understanding on the structure-activity relationship, which will be useful for new antimicrobial peptide designs and optimizations.