title: N-terminal amphipathic helix as a trigger of hemolytic activity in antimicrobial peptides: a case study in latarcins.
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.
authors: M.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
authors: Anton A
authors: AA
authors: Polyansky
authors: Alexander A
authors: AA
authors: Vassilevski
authors: Pavel E
authors: PE
authors: Volynsky
authors: Olga V
authors: OV
authors: Vorontsova
authors: Olga V
authors: OV
authors: Samsonova
authors: Natalya S
authors: NS
authors: Egorova
authors: Nicolay A
authors: NA
authors: Krylov
authors: Alexei V
authors: AV
authors: Feofanov
authors: Alexander S
authors: AS
authors: Arseniev
authors: Eugene V
authors: EV
authors: Grishin
authors: Roman G
authors: RG
authors: Efremov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006461:Hemolysis; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D013111:Spider Venoms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D013111:Spider Venoms