title: Dimerization of the antimicrobial peptide arenicin plays a key role in the cytotoxicity but not in the antibacterial activity.
abstract: The β-hairpin antimicrobial peptides arenicins from marine polychaeta Arenicola marina exhibit a broad spectrum of antimicrobial activity and high cytotoxicity. In this study the biological activities of arenicin-1 and its therapeutically valuable analog Ar-1[V8R] were investigated. The peptide Ar-1[V8R] displays significantly reduced cytotoxicity against mammalian cells relative to the wild-type arenicin-1. At the same time, both peptides exhibit similar antibacterial activities and kinetics of bacterial membrane permeabilization. Comparative NMR analysis of the peptides spatial structures in water and membrane-mimicking environment showed that Ar-1[V8R] in contrast to arenicin has significantly lower dimerization propensity. Thus, dimerization of the antimicrobial peptide arenicin plays a key role in the cytotoxicity but not in the antibacterial activity.
authors.affiliation: M.M.Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia.
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Panteleev
authors.affiliation: M.M.Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia.
authors.forename: Mikhail Yu
authors.initials: MY
authors.lastname: Myshkin
authors.affiliation: M.M.Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia.
authors.forename: Zakhar O
authors.initials: ZO
authors.lastname: Shenkarev
authors.affiliation: M.M.Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia. Electronic address: ovch@ibch.ru.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Ovchinnikova
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D015801:Helminth Proteins / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008555:Melitten / Q000737:chemistry; D008567:Membranes, Artificial; D008823:Micelles; D008826:Microbial Sensitivity Tests; D011994:Recombinant Proteins / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D015801:Helminth Proteins; D008567:Membranes, Artificial; D008823:Micelles; D011994:Recombinant Proteins; C496888:arenicin-1, Arenicola marina; D014867:Water; D008555:Melitten
keywords: Antimicrobial peptide; Arenicin; Cytotoxicity; Dimerization; NMR; Recombinant expression