1.D.193. The Amphiphilic Antimicrobial β-Stranded [KL]n Peptide ([KL]nP) Family
Amphipathic peptides can act as antibiotics due to membrane permeabilization. KL peptides with the repetitive sequence [Lys-Leu]n-NH2 form amphipathic beta-strands in the presence of lipid bilayers that kill bacteria in a length-dependent manner, by a "carpet" mechanism (Schweigardt et al. 2022). The activities of KL peptides with lengths from 6-26 amino acids (plus some inverted LK analogues) were tested against bacteria and erythrocytes. Vesicle leakage assays served to correlate bilayer thickness and peptide length. KL peptides with 10-12 amino acids showed the best therapeutic potential, i.e., high antimicrobial activity and low hemolytic side effects. The KL backbone lies flat on the membrane surface under all conditions, refuting a pore model. The length-dependent optimum for activity can be explained by two counteracting effects, membrane binding versus amyloid formation (Schweigardt et al. 2022).