Antimicrobial activity and protection from triton X-100-induced mammalian cell membrane lysis by artificial amphiphilic peptides

Abstract

Amphiphilic antimicrobial peptides play an important role in the innate immune system of various organisms. The peptides act mostly in α-helical or β-sheet structure to attack bacterial cell membrane, and have been attracted attention because they do not give rise to drug-resistant bacteria. Here we show the design of artificial amphiphilic peptides in poly-L-proline type-II helix structure, and assessed their antimicrobial activity. (Pro-Hyp-Gly)n-(Lys-Leu-Gly-Lys-Hyp- Gly)m-(Pro-Hyp-Gly) n [K2mLm], where n = 1-3 and 2m = 10- 2n, showed not only lysis of the bacterial cell membrane model liposome, which consists of dipalmytoyl phosphatidylglycerol (PG), but also remarkable protection against lysis of the mammalian cell membrane model liposome, which consists of phosphatidylcholine (PC). K8L4 showed EC50 nearly equal to 10 μg/mL for the lysis of PG liposome. K2mLm revealed to have bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus, and protection from cell membrane lysis of normal human dermal fibroblasts induced by triton X- 100. These artificial amphiphilic peptides in poly(Pro)II helix structure provide novel era for highly bacteria membrane selective antimicrobials. © 2011 Springer-Verlag Berlin Heidelberg.