title: Acipensins - Novel Antimicrobial Peptides from Leukocytes of the Russian Sturgeon Acipenser gueldenstaedtii.
abstract: Antimicrobial peptides (AMPs) play an important role in the innate defense mechanisms in humans and animals. We have isolated and studied a set of antimicrobial peptides from leukocytes of the Russian sturgeon Acipenser gueldenstaedtii belonging to a subclass of chondrosteans, an ancient group of bony fish. Structural analysis of the isolated peptides, designated as acipensins (Ac), revealed in leukocytes of the Russian sturgeon six novel peptides with molecular masses of 5336.2 Da, 3803.0 Da, 5173.0 Da, 4777.5 Da, 5449.4 Da, and 2740.2 Da, designated as Ac1-Ac6, respectively. Complete primary structures of all the isolated peptides were determined, and the biological activities of three major components - Ac1, Ac2, and Ac6 - were examined. The peptides Ac1, Ac2, Ac3, Ac4, and Ac5 were found to be the N-terminal acetylated fragments 1-0, 1-5, 1-9, 1-4, and 1-1 of the histone H2A, respectively, while Ac6 was shown to be the 62-5 fragment of the histone H2A. The peptides Ac1 and Ac2 displayed potent antimicrobial activity towards Gram-negative and Gram-positive bacteria (Escherichia coli ML35p, Listeria monocytogenes EGD, MRSA ATCC 33591) and the fungus Candida albicans 820, while Ac6 proved effective only against Gram-negative bacteria. The efficacy of Ac 1 and Ac2 towards the fungus and MRSA was reduced upon an increase in the ionic strength of the solution. Ac1, Ac2, and Ac6, at concentrations close to their minimum inhibitory concentrations, enhanced the permeability of the E.coli ML35p outer membrane to the chromogenic marker, but they did not affect appreciably the permeability of the bacterial inner membrane in comparison with a potent pore-forming peptide, protegrin 1. Ac1, Ac2, and Ac6 revealed no hemolytic activity against human erythrocytes at concentrations of 1 to 40 μM and had no cytotoxic effect (1 to 20 μM) on K-562 and U-937 cells in vitro. Our findings suggest that histone-derived peptides serve as important anti-infective host defense molecules.
authors.affiliation: Institute of Experimental Medicine, Northwest Branch of the Russian Academy of Medical Sciences, Academician Pavlov Street, 12, Saint-Petersburg 197376, Russia ; Saint-Petersburg State University, Universitetskaya Embankment, 7/9, Saint-Petersburg 199034, Russia.
authors.forename: O V
authors.initials: OV
authors.lastname: Shamova
authors.affiliation: Institute of Experimental Medicine, Northwest Branch of the Russian Academy of Medical Sciences, Academician Pavlov Street, 12, Saint-Petersburg 197376, Russia ; Saint-Petersburg State University, Universitetskaya Embankment, 7/9, Saint-Petersburg 199034, Russia.
authors.forename: D S
authors.initials: DS
authors.lastname: Orlov
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia ; Moscow Institute of Physics and Technology (State University), Department of Physicochemical Biology and Biotechnology, Institutskii Pereulok, 9, Dolgoprudny 141700, Moscow Region, Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Balandin
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia.
authors.forename: E I
authors.initials: EI
authors.lastname: Shramova
authors.affiliation: Saint-Petersburg State University, Universitetskaya Embankment, 7/9, Saint-Petersburg 199034, Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Tsvetkova
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia.
authors.forename: P V
authors.initials: PV
authors.lastname: Panteleev
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia.
authors.forename: Yu F
authors.initials: YF
authors.lastname: Leonova
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Tagaev
authors.affiliation: Institute of Experimental Medicine, Northwest Branch of the Russian Academy of Medical Sciences, Academician Pavlov Street, 12, Saint-Petersburg 197376, Russia ; Saint-Petersburg State University, Universitetskaya Embankment, 7/9, Saint-Petersburg 199034, Russia.
authors.forename: V N
authors.initials: VN
authors.lastname: Kokryakov
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia ; Moscow Institute of Physics and Technology (State University), Department of Physicochemical Biology and Biotechnology, Institutskii Pereulok, 9, Dolgoprudny 141700, Moscow Region, Russia.
authors.forename: T V
authors.initials: TV
authors.lastname: Ovchinnikova
keywords: acipensin; antimicrobial peptides; histone H2A derivatives; innate immunity; sturgeon leukocytes