In silico structural analyses of sets of α-helical antimicrobial peptides (AMPs) are performed. Differences between hemolytic and non-hemolytic AMPs are revealed in organization of their N-terminal region. A parameter related to hydrophobicity of the N-terminal part is proposed as a measure of the peptide propensity to exhibit hemolytic and other unwanted cytotoxic activities. Based on the information acquired, a rational approach for selective removal of these properties in AMPs is suggested. A proof of concept is gained through engineering specific mutations that resulted in elimination of the hemolytic activity of AMPs (latarcins) while leaving the beneficial antimicrobial effect intact. © 2009 Federation of European Biochemical Societies.
Polyansky, A. A., Vassilevski, A. A., Volynsky, P. E., Vorontsova, O. V., Samsonova, O. V., Egorova, N. S., … Efremov, R. G. (2009). N-terminal amphipathic helix as a trigger of hemolytic activity in antimicrobial peptides: A case study in latarcins. FEBS Letters, 583(14), 2425–2428. https://doi.org/10.1016/j.febslet.2009.06.044