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Published on: August 11, 2018
N-terminal amphipathic helix as a trigger of hemolytic activity in antimicrobial peptides: a case study in latarcins
Anton A Polyansky1, Alexander A Vassilevski, Pavel E Volynsky
1M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russsian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997 GSP, Moscow V-437, Russia. newant@gmail.com
Abstract:
In silico structural analyses of sets of alpha-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.
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