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Preference toward a polylysine enantiomer in inhibiting prions

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Abstract

Differential anti-prion activity of polylysine enantiomers was studied. Based on our recent discovery that poly-l-lysine (PLK) is a potent anti-prion agent, we investigated suppression of prions in cultured cells using poly-d-lysine (PDK). The results showed that PDK was more efficacious than PLK to inhibit prions. Protein misfolding cyclic amplification assay demonstrated improved efficacy of PDK in inhibiting plasminogen-mediated prion propagation, corresponding to the enantio-preference of PDK observed in cultured cells. Furthermore, our study demonstrated that polylysines formed a complex with plasminogen. These results propose to hypothesize a plausible mechanism that elicits prion inhibition by polylysine enantiomers.

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References

  • Arnold LJJ, Dagan A, Gutheil J, Kaplan NO (1979) Antineoplastic activity of poly(l-lysine) with some ascites tumor cells. Proc Natl Acad Sci USA 76:3246–3250

    Article  PubMed  CAS  Google Scholar 

  • Bae Y, Fukushima S, Harada A, Kataoka K (2003) Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change. Angew Chem Int Ed Engl 42(38):4640–4643

    Article  PubMed  CAS  Google Scholar 

  • Banecerraf B, Levine BB (1964) The relationship between in vivo and in vitro enzymatic degradabilityof hapten-polylysine conjugates and their antigenicities in guinea pigs. J Exp Med 120:955–965

    Article  Google Scholar 

  • Butler DA, Scott MRD, Bockman JM, Borchelt DR, Taraboulos A, Hsiao KK, Kingsbury DT, Prusiner SB (1988) Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins. J Virol 62:1558–1564

    PubMed  CAS  Google Scholar 

  • Clarke MC, Haig DA (1970) Evidence for the multiplication of scrapie agent in cell culture. Nature 225:100–101

    Article  PubMed  CAS  Google Scholar 

  • David JT (1997) Stereoselectivity of drug action. Drug Discov Today 2(4):138–147

    Article  Google Scholar 

  • Greenfield N, Fasman GD (1969) Computed circular dichroism spectra for the evaluation of protein conformation. Biochemistry 8:4108–4116

    Article  PubMed  CAS  Google Scholar 

  • Hatton MW, Regoeczi E (1975) The relevance of the structure of lysine bound to Sepharose for the affinity of rabbit plasminogen. Biochim Biophys Acta 379(2):504–511

    Article  PubMed  CAS  Google Scholar 

  • Langeland N, Moore LJ, Holmsen H, Haarr L (1988) Interaction of polylysine with the cellular receptor for herpes simplex virus type 1. J Gen Virol 69(6):1137–1145

    Article  PubMed  CAS  Google Scholar 

  • Lim Y-b, Mays CE, Kim Y, Titlow WB, Ryou C (2010) The inhibition of prions through blocking prion conversion by permanently charged branched polyamines of low cytotoxicity. Biomaterials 31(8):2025–2033

    Article  PubMed  CAS  Google Scholar 

  • Luo D, Saltzman WM (2000) Synthetic DNA delivery systems. Nat Biotech 18(1):33–37

    Article  CAS  Google Scholar 

  • Mays CE, Ryou C (2010) Plasminogen stimulates propagation of protease-resistant prion protein in vitro. FASEB J 24(12):5102–5112

    Article  PubMed  CAS  Google Scholar 

  • Mays CE, Kang H-E, Kim Y, Shim SH, Bang J-E, Woo H-J, Cho Y-H, Kim J-B, Ryou C (2008) CRBL cells: establishment, characterization and susceptibility to prion infection. Brain Res 1208:170–180

    Article  PubMed  CAS  Google Scholar 

  • Mays CE, Titlow W, Seward T, Telling GC, Ryou C (2009) Enhancement of protein misfolding cyclic amplification by using concentrated cellular prion protein source. Biochem Biophys Res Commun 388(2):306–310

    Article  PubMed  CAS  Google Scholar 

  • Park SH, Raines RT (2004) Fluorescence gel retardation assay to detect protein–protein interactions. Methods Mol Biol 261:155–160

    PubMed  CAS  Google Scholar 

  • Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95:13363–13383

    Article  PubMed  CAS  Google Scholar 

  • Ryou C (2007) Prions and prion diseases: fundamentals and mechanistic details. J Microbiol Biotechnol 17(7):1059–1070

    PubMed  CAS  Google Scholar 

  • Ryou C (2010) Transmissible spongiform encephalopathy. In: Saleh M (ed) Molecular aspects of infectious diseases. Nova Science Publisher, Hauppauge, pp 151–172

    Google Scholar 

  • Ryou C (2011) Prion diseases. Encyclopedia of Life Sciences. Wiley, Chichester. doi:10.1002/9780470015902.a0000428.pub2

  • Ryou C, Mays CE (2010) Prions. In: Saleh M (ed) Molecular aspects of infectious diseases. Nova Science Publisher, Hauppauge, pp 129–149

    Google Scholar 

  • Ryou C, Legname G, Peretz D, Craig JC, Baldwin MA, Prusiner SB (2003) Differential inhibition of prion propagation by enantiomers of quinacrine. Lab Invest 83:837–843

    PubMed  CAS  Google Scholar 

  • Ryou C, Titlow WB, Mays CE, Bae Y, Kim S (2011) The suppression of prion propagation using poly-l-lysine by targeting plasminogen that stimulates prion protein conversion. Biomaterials 32(11):3141–3149

    Article  PubMed  CAS  Google Scholar 

  • Saborio GP, Permanne B, Soto C (2001) Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411:810–813

    Article  PubMed  CAS  Google Scholar 

  • Shima S, Matsuoka H, Iwamoto T, Sakai H (1984) Antimicrobial action of epsilon-poly-l-lysine. J Antibiot 37(11):1449–1455

    Article  PubMed  CAS  Google Scholar 

  • Sodetz JM, Brockway WJ, Castellino FJ (1972) Multiplicity of rabbit plasminogen: physical characterisation. Biochem 11(24):4451–4458

    Article  CAS  Google Scholar 

  • Supattapone S, Nguyen H-OB, Cohen FE, Prusiner SB, Scott MR (1999) Elimination of prions by branched polyamines and implications for therapeutics. Proc Natl Acad Sci USA 96(25):14529–14534

    Article  PubMed  CAS  Google Scholar 

  • Supattapone S, Wille H, Uyechi L, Safar J, Tremblay P, Szoka FC, Cohen FE, Prusiner SB, Scott MR (2001) Branched polyamines cure prion-infected neuroblastoma cells. J Virol 75:3453–3461

    Article  PubMed  CAS  Google Scholar 

  • Tsuyuki E, Tsuyuki H, Stahmann MA (1956) The synthesis and enzymatic hydrolysis of poly-d-lysine. J Biol Chem 222:479–485

    PubMed  CAS  Google Scholar 

  • Xu Z, Adrover M, Pastore A, Prigent S, Mouthon F, Comoy E, Rezaei H, Deslys JP (2011) Mechanistic insights into cellular alteration of prion by poly-d-lysine: the role of H2H3 domain. FASEB J 25(10):3426–3435

    Article  PubMed  CAS  Google Scholar 

  • Yavin E, Yavin Z (1974) Attachment and culture of dissociated cells from rat embryo cerebral hemispheres on polylysine-coated surface. J Cell Biol 62(2):540–546

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank P. Thomason for editorial and H. Lee for technical assistance.

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The authors declare that we have no conflict of interest.

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Correspondence to Chongsuk Ryou.

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K. S. Jackson and J. Yeom contributed equally to this work.

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Jackson, K.S., Yeom, J., Han, Y. et al. Preference toward a polylysine enantiomer in inhibiting prions. Amino Acids 44, 993–1000 (2013). https://doi.org/10.1007/s00726-012-1430-8

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  • DOI: https://doi.org/10.1007/s00726-012-1430-8

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