Synthetic Antimicrobial Peptides. II. Antimicrobial and Hemolytic Activity of Cationic Peptides Containing Cysteine Residues with Free Sulfhydryl Groups

The antimicrobial and hemolytic activities of R9F2C2 (P1ss), (KFF)(3)KC2 (P2ss), and (RAhaR)(4)Aha beta AC(2) (P3ss) (where Aha is 6-aminohexanoic acid and beta A is beta-alanine) synthetic antimicrobial peptides (SAMP) with different amphipathic properties and containing the cysteine residues with free sulfhydryl groups were studied. The introduction of cysteine residues into the composition of SAMP was shown to increase their antimicrobial activity 3-7 times, while their hemolytic activity increased 2-12 times in relation to human erythrocytes for different peptides in different ways, which determined their different selectivity. The P1ss peptide with a linear type of amphipathicity showed the highest antimicrobial activity and high selectivity against the fungus Candida albicans and bacterium Staphylococcus aureus (MIC 0.5 mu M; TI 52 mu M). The P1ss peptide possessed not only greater antimicrobial activity against pathogenic fungus C. albicans in comparison to the P2ss peptide (MIC 3.9 mu M) with the classical helical amphipathicity, but also more than three times lower hemolytic activity (MHC 26 and 8 mu M, respectively). Therefore, TI for the P2ss peptide (TI 2.1) turned out to be more than 20 times lower than that for the P1ss peptide. Thus, the P1ss peptide is the most promising antimicrobial preparation among the studied SAMP.