Antibacterial and Antifungal Activities of Linear and Cyclic Peptides Containing Arginine, Tryptophan, and Diphenylalanine

Abstract

Background. We have previously reported peptides composed of sequential arginine (R) residues paired with tryptophan (W) or 3,3-diphenyl-L-alanine residues (Dip), such as cyclic peptides [R4W4] and [R4(Dip)3], as antibacterial agents. Results. Herein, we report antibacterial and antifungal activities of five linear peptides, namely ((DipR)4(WR)), ((DipR)3(WR)2), ((DipR)2(WR)3), ((DipR)(WR)4), and (DipR)4R, and five cyclic peptides [(DipR)4(WR)], [(DipR)3(WR)2], [(DipR)2(WR)3], [(DipR)(WR)4], and [DipR]5, containing alternate positively charged R and hydrophobic W and Dip residues against fungal, Gram-positive, and Gram-negative bacterial pathogens. The minimum inhibitory concentrations (MICs) of all peptides were determined by the micro-broth dilution method against Methicillin-Resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus subtilis. Fungal organisms were Candida albicans, Candida parapsilosis, and Aspergillus fumigatus. [DipR]5 and ((DipR)2(WR)3) showed MIC values of 0.39–25 µM and 0.78–12.5 µM against Gram-positive and Gram-negative bacteria strains, respectively. The highest activity was observed against S. pneumoniae with MIC values of 0.39–0.78 µM among tested compounds. [DipR]5 demonstrated MIC values of 6.6 µM against C. parapsilosis and 1.6 µM against A. fumigatus, whereas fluconazole showed MIC values of 3.3 µM and >209 µM, respectively. Conclusions. These findings highlight the potential of these peptides as broad-spectrum antimicrobial agents.

Keywords

• antibiotic resistance
• antibiotics
• antifungal
• antimicrobial peptides
• arginine
• 3,3-Diphenyl-L-alanine