N-terminal amphipathic helix as a trigger of hemolytic activity in antimicrobial peptides: a case study in latarcins.
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.
Polyansky
Anton A
AA
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
Vassilevski
Alexander A
AA
Volynsky
Pavel E
PE
Vorontsova
Olga V
OV
Samsonova
Olga V
OV
Egorova
Natalya S
NS
Krylov
Nicolay A
NA
Feofanov
Alexei V
AV
Arseniev
Alexander S
AS
Grishin
Eugene V
EV
Efremov
Roman G
RG
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
D023181:Antimicrobial Cationic Peptides; D013111:Spider Venoms