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Mechanism of biological activity of short peptides: Cell penetration and epigenetic regulation of gene expression

Biology Bulletin Reviews volume 3, pages 451–455 (2013)Cite this article

Abstract

Data on various aspects of the molecular and cellular mechanism of the biological activity of short peptides used as potential drugs were analyzed. Based on the published data and our own results, a possible mechanism of the penetration of short peptides into the cytoplasm and cell nucleus is considered. In addition, the possibility of the involvement of short peptides in the mechanisms of the epigenetic regulation of gene expression via their complimentary interaction with promoter regions of genes in DNA is substantiated.

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References

  • Alberts, B., Bray, D., Lewis, J., Raf, M., Roberts, K., and Watson, J.D., Molecular Biology of the Cell, New York: Garland Science, 1994, pp. 561–563.

    Google Scholar 

  • Anisimov, V.N. and Khavinson, V.Kh., Peptide bioregulation of aging: results and prospects, Biogerontology, 2010, vol. 11, pp. 139–149.

    CAS  PubMed  Article  Google Scholar 

  • Ashmarin, I.P., Hormones and regulatory peptides: differences and resemblance of the concepts and functions. The place of hormones among other intercellular sensors, Ross. Khim. Zh., 2002, vol. 49, no. 1, pp. 4–7.

    Google Scholar 

  • Denisov, G., Wanaski, S., Luan, P. Glaser, M., and McLaughlin, S., Binding of basic peptides to membranes produces lateral domains enriched in the acidic lipids phosphatidylserine and phosphatidylinositol 4.5-bisphosphate: an electrostatic model and experimental results, Biophys. J., 1998, vol. 74, no. 2, pp. 731–744.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Deigin, V.I., Semenets, T.N., Zamulaeva, I.A., Maliutina, Y.V., Selivanova, E.I., Saenko, A.S., and Semina, O.V., The effects of the EW dipeptide optical and chemical isomers on the CFU-S population in intact and irradiated mice, Int. Immunopharmacol., 2007, vol. 7, no. 3, pp. 375–382.

    CAS  PubMed  Article  Google Scholar 

  • Du Vigneaud, V., Ressler, C., and Trippett, S., The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin, J. Biol. Chem., 1953, vol. 205, no. 12, pp. 949–957.

    CAS  Google Scholar 

  • Duchardt, F., Fotin-Mleczek, M., Schwarz, H., Fischer, R., and Brock, R., A comprehensive model for the cellular uptake of cationic cell-penetrating peptides, Traffic, 2007, vol. 8, pp. 848–866.

    CAS  PubMed  Article  Google Scholar 

  • Fedoreeva, L.I., Kireev, I.I., Khavinson, V.Kh., and Vanyushin, B.F., Penetration of short fluorescence labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA, Biochemistry, 2010, vol. 76, pp. 1210–1219.

    Google Scholar 

  • Fedoreeva, L.I. and Vanyushin, B.F., CNG site-specific and methyl-sensitive endonuclease WEN1 from wheat seedlings, Biochemistry, 2011, vol. 76, no. 6, pp. 651–657.

    Google Scholar 

  • Ferrer-Miralles, N., Vázquez, E., and Villaverde, A., Membrane-active peptides for non-viral gene therapy: making the safest easier, Trends Biotechnol., 2008, vol. 26, no. 5, pp. 267–275.

    CAS  PubMed  Article  Google Scholar 

  • Frankel, A.D. and Pabo, C.O., Cellular uptake of the tat protein from human immunodeficiency virus, Cell, 1988, vol. 55, pp. 1189–1193.

    CAS  PubMed  Article  Google Scholar 

  • Fuchs, S.M. and Raines, R.T., Pathway for polyargenine entry into mammalian cells, Biochemistry, 2004, vol. 43, pp. 2438–2444.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Futaki, S., Goto, S., and Sugiura, Y., Membrane permeability commonly shared among arginine-rich peptides, J. Mol. Recognit., 2003, vol. 16, no. 5, pp. 260–264.

    CAS  PubMed  Article  Google Scholar 

  • Ivanov, V.T. and Yatskin, O.N., Peptidomics: a logical sequel to proteomics, Expert. Rev. Proteomics, 2005, vol. 2, no. 4, pp. 463–473.

    CAS  PubMed  Article  Google Scholar 

  • Khavinson, V.Kh., Tissue-specific effects of peptides, Bull. Exp. Biol. Med., 2001, vol. 132, no. 8, pp. 807–808.

    CAS  PubMed  Article  Google Scholar 

  • Khavinson, V.Kh., US Patent 6727227, 2004.

  • Khavinson, V.Kh., US Patent 7101854, 2006.

  • Khavinson, V.Kh., Bondarev, I.E., and Butyugov, A.A., Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells, Bull. Exp. Biol. Med., 2003b, vol. 135, no. 6, pp. 590–592.

    CAS  PubMed  Article  Google Scholar 

  • Khavinson, V.Kh., Bondarev, I.E., Butyugov, A.A., and Smirnova, T.D., Peptide promotes overcoming of the division limit in human somatic cell, Bull. Exp. Biol. Med., 2004, vol. 137, no. 5, pp. 503–506.

    CAS  PubMed  Article  Google Scholar 

  • Khavinson, V.Kh., Grigoriev, E.I., Malinin, V.V., and Ryzhak, G.A., US Patent 7851449, 2010.

  • Khavinson, V.Kh., Grigoriev, E.I., Malinin, V.V., and Ryzhak, G.A., EEC Patent 2024388, 2009.

  • Khavinson, V.Kh., Khokkanen V.M., Trofimova S.V., and Malinin, V.V., tRF Patent 2177801, 2002.

  • Khavinson, V.Kh. and Malinin, V.V., Gerontological Aspects of Genome Peptide Regulation, Basel, Switzerland: Karger AG, 2005.

    Google Scholar 

  • Khavinson, V.Kh., Malinin, V.V., Grigoriev, E.I., and Ryzhak, G.A., US Patent 7491703, 2009a.

  • Khavinson, V.Kh., Malinin, V.V., and Ryzhak, G.A., EA Patent 010724, 2008a.

  • Khavinson, V.Kh., Malinin, V.V., and Ryzhak, G.A., EA Patent 010735, 2008b.

  • Khavinson, V.Kh., Morozov, V.G., Malinin, V.V., and Grigoriev, E.I., US Patent 7189701, 2007.

  • Khavinson, V.Kh., Ryzhak, G.A., Grigoriev, E.I., and Ryadnova, I.Yu., EEC Patent 1758922, 2008c.

  • Khavinson, V.Kh., Ryzhak, G.A., Grigoriev, E.I., and Ryadnova, I.Yu., US Patent 7625870, 2009b.

  • Khavinson, V.Kh., Ryzhak, G.A., Grigoriev, E.I., and Ryadnova, I.Yu., EEC Patent 1758923, 2008d.

  • Khavinson, V.Kh., Serv, S.V., and Morozov, V.G., US Patent 6139862, 2000.

  • Khavinson, V.Kh., Shataeva, L.K., and Bondarev, I.E., A model of interaction between regulatory peptides and DNA double helix, Usp. Sovrem. Biol., 2003c, vol. 123, no. 5, pp. 467–474.

    CAS  Google Scholar 

  • Khavinson, V.Kh., Shataeva, L.K., and Chernova, A.A., Effect of regulatory peptides on gene transcription, Bull. Exp. Biol. Med., 2003a, vol. 136, no. 3, pp. 288–290.

    CAS  PubMed  Article  Google Scholar 

  • Khavinson, V.Kh., Solovyev, A.Yu., Zhilinski, D.V., Shataeva, L.K., and Vanyushin, B.F., Epigenetic aspects of aging peptide regulation, Usp. Gerontol., 2012, vol. 25, no. 1, pp. 11–16.

    Google Scholar 

  • Kubo, T. and Yokoyama, R., Structure and affinity of DNA binding peptides, Nucleic Acids Symp. Ser., 2000, no. 44, pp. 49–50.

    Google Scholar 

  • Kyte, J. and Doolittle, R.F., A simple method for displaying the hydropathic character of a protein, J. Mol. Biol., 1982, vol. 157, no. 1, pp. 105–132.

    CAS  PubMed  Article  Google Scholar 

  • Lindgren, V. and Hallbrink, M., Cell-penetrating peptides, Trends Pharmacol. Sci., 2000, vol. 21, pp. 99–103.

    CAS  PubMed  Article  Google Scholar 

  • Martin, M.E. and Rice, K.G., Peptide-guided gene delivery, AAPS J., 2007, vol. 9, no. 1, pp. 18–29.

    Article  Google Scholar 

  • Morozov, V.G. and Khavinson, V.Kh., US Patent 5814611, 1998.

  • Morris, M.C. and Depollier, J., A peptide carrier for the delivery of biologically active proteins into mammalian cells, Nat. Biotechnol., 2001, vol. 19, pp. 1173–1176.

    CAS  PubMed  Article  Google Scholar 

  • Myasoedov, N.F., Andreeva, L.A., Lyapina, L.A., Ulyanov, A.M., Shubina, T.A., Obergan, T.Y., Pastorova, V.E., and Grigorieva, M.E., The combined antidiabetogenic and anticoagulation effects of tripeptide Gly-Pro-Arg as estimated in the model of persistent hyperglycemia in rats, Dokl. Biol. Sci., 2011, vol. 438, pp. 135–137.

    CAS  PubMed  Article  Google Scholar 

  • Ohno, M., Fornered, M., and Mattaj, I.W., Nucleocytoplasmic transport: the last 200 nanometers, Cell, 1998, vol. 92, no. 2, pp. 327–336.

    CAS  PubMed  Article  Google Scholar 

  • Ostrovskaya, R.U., Gruden, M.A., Bobkova, N.A., Sewell, R.D., Gudasheva, T.A., Samokhin, A.N., Seredinin, S.B., Noppe, W., Sherstnev, V.V., and Morozova-Roche, L.A., The nootropic and neuroprotective prolinecontaining dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer’s disease model, J. Psychopharmacol., 2007, vol. 6, pp. 611–619.

    Google Scholar 

  • Romanov, G.A., Naumkina, E.M., Ashapkin, V.V., and Vanyushin, B.F., Methylation of GCGG sites of the patatin promoter is organ-specific and inversely correlates with its activity, Dokl. Biochem. Biophys., 2007, vol. 417, pp. 327–330.

    CAS  PubMed  Article  Google Scholar 

  • Sokolova, O.S., Shaitan, K.V., Grizel, A.V., Popinako, A.V., Karlova, M.G., and Kirpichhikov, M.P., Three-dimensional structure of human voltage-gated ion channel Kv10.2 studied by electron microscopy of macromolecules and molecular modeling, Russ. J. Bioorg. Chem., 2012, vol. 38, no. 2, pp. 152–158.

    CAS  Article  Google Scholar 

  • Vanyushin, B.F., Materialization of epigenetics or insignificant changes of DNA with great consequences, Khim. Zhizn’, 2004, no. 2, pp. 32–37.

    Google Scholar 

  • Vanyushin, B.F. and Ashapkin, V.V., DNA methylation in higher plants: past, present and future, Biochim. Biophys. Acta, 2011, vol. 1809, no. 8, pp. 360–368.

    CAS  PubMed  Article  Google Scholar 

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Authors and Affiliations

  1. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia

    V. Kh. Khavinson

  2. St. Petersburg Institute of Bioregulation and Gerontology, St. Petersburg, Russia

    V. Kh. Khavinson, A. Yu. Solov’ev, S. I. Tarnovskaya & N. S. Lin’kova

Authors
  1. V. Kh. Khavinson
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  2. A. Yu. Solov’ev
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  3. S. I. Tarnovskaya
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  4. N. S. Lin’kova
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Correspondence to V. Kh. Khavinson.

Additional information

Original Russian Text © V.Kh. Khavinson, A.Yu. Solov’ev, S.I. Tarnovskaya, N.S. Lin’kova, 2013, published in Uspekhi Sovremennoi Biologii, 2013, Vol. 133, No. 3, pp. 310–316.

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Khavinson, V.K., Solov’ev, A.Y., Tarnovskaya, S.I. et al. Mechanism of biological activity of short peptides: Cell penetration and epigenetic regulation of gene expression. Biol Bull Rev 3, 451–455 (2013). https://doi.org/10.1134/S2079086413060042

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  • DOI: https://doi.org/10.1134/S2079086413060042

Keywords

  • short peptides
  • penetration into the cell
  • epigenetic regulation of gene expression