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Synthesis, conformation and cytotoxicity of new, branched polymeric polypeptides containing hydrophobic amino acid or arginine moiety

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Abstract

In this paper we report on the synthesis and solution conformation of a new set of structurally related polycationic branched chain polypeptides (poly[Lys(X i -dl-Ala m )]) with hydrophobic (Ile, Nle, Val) or cationic (Arg) amino acids at the N-terminal end of the side chains as well as their cytotoxic effect on murine bone marrow derived macrophages. Solution conformation of the polypeptides was studied with circular dichroism spectroscopy under different conditions (pH, ionic strength). The results of these comparative studies indicate that a) polypeptides could adopt an ordered (mainly helical) conformation at physiological pH and salt concentration (pH 7.4, 0.2 M NaCl); b) the nature of side chain terminal amino acid (X) could determine under which conditions the ordered structure was formed. Thus, the solution conformation of branched polypeptides could be modulated by the selection of amino acid X under physiological conditions. All polypeptides with hydrophobic amino acid at the terminal position were essentially non-toxic on macrophages, whereas the polypeptide with terminal Arg proved to be markedly cytotoxic.

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Acknowledgments

This work was supported by a grant from the Hungarian National Research Fund (OTKA K104385). R. Szabó (PhD) was supported by the Postdoctoral Fellowship of Hungarian Academy of Sciences (HAS). The authors thank Dr. Zsuzsa Majer for the helpful discussion concerning the interpretation of CD spectra. The authors also thank Dr. Hedvig Medzihradszky-Schweiger for the amino acid analyses.

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Authors and Affiliations

  1. MTA-ELTE Research Group of Peptide Chemistry, Pázmány P. sétány 1/A, Budapest, H-1117, Hungary

    Mónika Sebestyén, Rita Szabó, Gábor Mező, György Kóczán & Ferenc Hudecz

  2. Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest, H-1085, Hungary

    László Kőhidai & Éva Pállinger

  3. ELTE Department of Organic Chemistry, Pázmány P. sétány 1/A, Budapest, H-1117, Hungary

    Ferenc Hudecz

Authors
  1. Mónika Sebestyén
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  2. Rita Szabó
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  3. László Kőhidai
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  4. Éva Pállinger
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  5. Gábor Mező
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  6. György Kóczán
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  7. Ferenc Hudecz
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Corresponding author

Correspondence to Ferenc Hudecz.

Additional information

Mónika Sebestyén and Rita Szabó contributed equally to this study.

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Sebestyén, M., Szabó, R., Kőhidai, L. et al. Synthesis, conformation and cytotoxicity of new, branched polymeric polypeptides containing hydrophobic amino acid or arginine moiety. Struct Chem 28, 527–535 (2017). https://doi.org/10.1007/s11224-016-0901-z

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  • DOI: https://doi.org/10.1007/s11224-016-0901-z

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