Antimicrobial peptides (AMPs), a major class of antibacterial agents, share amphiphilicity and cationic structural properties with cell-penetrating peptides (CPPs). Herein, several amphiphilic cyclic and linear CPPs containing tryptophan and arginine along with their analogs were synthesized and exhibited potent antibacterial activities against multidrug resistant pathogens. Among them, a cyclic peptide containing arginine and tryptophan namely [R4W4] showed the highest antibacterial potency against methicillin-resistant Staphylococcus aureus (MRSA, exhibiting a minimum inhibitory concentration (MIC) of 2.67 �g/mL). Furthermore, the cyclic [R4W4] peptide and its linear counterpart R4W4 exhibited the MIC values of 42.8 and 21.7 �g/mL, respectively, against Pseudomonas aeruginosa. Cyclic [R4W4] also showed cell-penetrating property as expected. This peptide exhibited less than 16% cytotoxicity at 15 �M (20.5 �g/mL) concentration in three different human cell lines. This study suggests that there is a strong correlation between cell penetrating and antimicrobial properties in this class of amphiphilic peptides.

Antibacterial activities of amphiphilic cyclic cell-penetrating peptides against multidrug resistant pathogens

248th National Meeting (2014)

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