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). 




Schweigardt, F., E. Strandberg, P. Wadhwani, J. Reichert, J. Bürck, H.L.P. Cravo, L. Burger, and A.S. Ulrich. (2022). Membranolytic Mechanism of Amphiphilic Antimicrobial β-Stranded [KL] Peptides. Biomedicines 10:.