Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1067810.32607/20758251-2011-3-2-68-78ArticlesСтатьиResearch ArticleN-Terminal Moiety of Antimicrobial Peptide Ltc1-K Increases its Toxicity for Eukaryotic CellsN-Terminal Moiety of Antimicrobial Peptide Ltc1-K Increases its Toxicity for Eukaryotic CellsSamsonovaO VKudryashovaK SFeofanovA Vavfeofanov@yandex.ruLomonosov Moscow State UniversityShemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesLomonosov Moscow State UniversityShemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences1506201132VOL 3, NO2 (2011)ТОМ 3, №2 (2011)687817012020Copyright ©; 2011, Samsonova O.V., Kudryashova K.S., Feofanov A.V.Copyright ©; 2011, Samsonova O.V., Kudryashova K.S., Feofanov A.V.2011Samsonova O.V., Kudryashova K.S., Feofanov A.V.Samsonova O.V., Kudryashova K.S., Feofanov A.V.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10678

The antimicrobial peptide Ltc1-K and its derivates without one, two, then three N-terminal amino acid residues were studied based on the hypothesis (backed by some experimental data) that the hydrophobic N-terminal moiety of linear cationic antimicrobial peptides defines their haemolytic activity. It was discovered that the excision of three N-terminal amino acid residues considerably decreases the peptide’s toxicity for eukaryotic cells and simultaneously increases the selectivity of antibacterial activity for some bacteria species. Studies performed with the model membrane systems and human erythrocytes revealed that the main reason for the observed effect is a multifold decrease in the peptide’s affinity to an eukaryotic cellular membrane enriched with zwitterionic phospholipids.

antimicrobial peptideslatarcinhaemolytic activitycircular dichroismfluorescent confocal microscopyHancock R.E.W., Chapple S.D. // Antimicrob. Agents Chemother. 1999. V. 43. P. 1317-1323.Finlay B.B., Hancock R.E.W. // Nat. Rev. Microbiol. 2004. V. 2. P. 497-504.Jenssen H., Hamill P., Hancock R.E.W. // Clin. Microbiol. Rev. 2006. V. 19. P. 491-511.Kozlov S.A., Vassilevski A.A., Feofanov A.V., Surovoy A.Y., Karpunin D.V., Grishin E.V. // J. Biol. Chem. 2006. V. 281. P. 20983-20992.Polyansky A.A., Vassilevski A.A., Volynsky P.E., Vorontsova O.V., Samsonova O.V., Egorova N.S., Krylov N.A., Feofanov A.V., Arseniev A.S., Grishin E.V., et al. // FEBS Lett. 2009. V. 583. P. 2425-2428.Vassilevski A. A., Kozlov S. A., Zhmak M. N., Kudelina I. A., Dubovskii P. V., Shatursky O. Ya., Arseniev A. S., Grishin E. V. // Bioorg. Khim. 2007. V. 33. P. 405-412.Dubovskii P.V., Volynsky P.E., Polyansky A.A., Karpunin D.V., Chupin V.V., Efremov R.G., Arseniev A. S. // Biochemistry. 2008. V. 47. P. 3525-3533.Provencher S.W., Glockner J. // Biochemistry. 1982. V. 20. P. 33-37.Vassilevski A.A., Kozlov S.A., Samsonova O.V., Egorova N.S., Karpunin D.V., Pluzhnikov K.A., Feofanov A.V., Grishin E.V. // Biochem. J. 2008. V. 411. P. 687-696.Seelig J. // Biochim. Biophys. Acta. 2004. V. 1666. P. 40-50.Brogden K.A. // Nat. Rev. Microbiol. 2005. V. 3. P. 238-250.White S.H., Whimley W.C. // Annu. Rev. Biophys. Biomol. Struct. 1999. V. 28. P. 319-365.Yuan P., Fisher P.J., Prendergast F.G., Kemple M.D. // Biophys. J. 1996. V. 70. P. 2223-2238.Strandberg E., Ulrich A. // Concepts Magn. Reson. Part A. Bridg. Educ. Res. 2004. V. 23. P. 89-120.Fernandez D.I., Gehman J.D., Separovic F. // Biochim. Biophys. Acta. 2009. V. 1788. P. 1630-1638.Dathe M., Wieprecht T. // Biochim. Biophys. Acta. 1999. V. 1462. P. 71-87.Armstrong J.K., Wenby R.B., Meiselman H.J., Fisher T.C. // Biophys. J. 2004. V. 87. P. 4259-4270.Sheetz M.P., Singer S.J.J. // J. Cell Biol. 1976. V. 70. P. 247-251.Evans E.A. // Biophys. J. 1974. V. 14. P. 923-931.Iglič A., Kralj-Iglič V., Hägerstrand H. // Eur. Biophys. J. 1998. V. 27. P. 335-339.Lim G.H.W., Wortis M., Mukhopadhyay R. // Proc. Natl. Acad. Sci. USA. 2002. V. 99. P. 16766-16769.Isomaa B., Hägerstrand H., Paatero G. // Biochim. Biophys. Acta. 1987. V. 899. P. 93-103.Semrau S., Monster M.W., van der Knaap M., Florea B.I., Schmidt T., Overhand M. // Biochim. Biophys. Acta. 2010. V. 1798. P. 2033-2039.