Membranolytic Mechanism of Amphiphilic Antimicrobial β-Stranded [KL] Peptides.

Amphipathic peptides can act as antibiotics due to membrane permeabilization. KL peptides with the repetitive sequence [Lys-Leu]-NH form amphipathic β-strands in the presence of lipid bilayers. As they are known to kill bacteria in a peculiar length-dependent manner, we suggest here several different functional models, all of which seem plausible, including a carpet mechanism, a β-barrel pore, a toroidal wormhole, and a β-helix.

Phosphate-dependent aggregation of [KL] peptides affects their membranolytic activity.

In this study, we investigate how the length of amphiphilic β-sheet forming peptides affects their interaction with membranes. Four polycationic model peptides with lengths from 6 to 18 amino acids were constructed from simple Lys-Leu repeats, giving [KL]. We found that (1) they exhibit a pronounced antimicrobial activity with an intriguing length dependent maximum for [KL] with 10 amino acids; (2) their hemolytic effect, on the other hand, increases steadily with peptide length.