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Compatibility of the conformationally rigid CF3-Bpg side chain with the hydrophobic coiled-coil interface

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Abstract

3-(Trifluoromethyl)bicyclopent-[1.1.1]-1-yl glycine (CF3-Bpg) has previously been established as a useful 19F NMR label to analyse the structures of oligomeric membrane-active peptides or transmembrane segments. To systematically examine the effect of side chain volume, conformational rigidity, and hydrophobicity of CF3-Bpg in polypeptide environments the amino acid was incorporated into an established coiled-coil based screening system. A single substitution of either valine (position a16) or leucine (position d19) within the hydrophobic core of the heteromeric coiled coil has practically no effect on its structure. Despite its comparatively high hydrophobicity, however, the stiff and bulky side chain of CF3-Bpg is not so well accommodated by the hydrophobic core as it leads to a more pronounced destabilization than observed for other, more polar fluorinated amino acids which carry more flexible side chains. CF3-Bpg is therefore a useful 19F NMR label, though not for monitoring the stability of such helix–helix interactions.

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References

  • Afonin S, Mikhailiuk PK, Komarov IV, Ulrich AS (2007) Evaluating the amino acid CF3-bicyclopentylglycine as a new label for solid-state 19F NMR structure analysis of membrane-bound peptides. J Pept Sci 13:614–623

    Article  CAS  PubMed  Google Scholar 

  • Afonin S, Grage SL, Ieronimo M, Wadhwani P, Ulrich AS (2008) Temperature-dependent transmembrane insertion of the amphiphilic peptide PGLa in lipid bilayers observed by solid state 19F NMR spectroscopy. J Am Chem Soc 130:16512–16514

    Article  CAS  PubMed  Google Scholar 

  • Carpino LA, El-Faham A (1999) The diisopropylcarbodiimide/1-hydroxy-7-azabenzotriazole system: segment coupling and stepwise peptide assembly. Tetrahedron 55:6813–6830

    Article  CAS  Google Scholar 

  • Cobb SL, Murphy CD (2009) 19F NMR applications in chemical biology. J Fluorine Chem 130:132–143

    Article  CAS  Google Scholar 

  • Fields GB, Noble RL (1990) Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res 35:161–214

    Article  CAS  PubMed  Google Scholar 

  • Grage SL, Afonin S and Ulrich AS (2010) Dynamic transitions of membrane-active peptides. In: Giuliani A, Rinaldi AC (eds) Antimicrobial peptides: methods and protocols, vol 618. Springer, Heidelberg, pp 183–207

  • Jäckel C, Koksch B (2005) Fluorine in peptide design and protein engineering. Eur J Org Chem 2005:4483–4503

    Article  Google Scholar 

  • Jäckel C, Seufert W, Thust S, Koksch B (2004) Evaluation of the molecular interactions of fluorinated amino acids with native polypeptides. ChemBioChem 5:717–720

    Article  PubMed  Google Scholar 

  • Jäckel C, Salwiczek M, Koksch B (2006) Fluorine in a native protein environment—how the spatial demand and polarity of fluoroalkyl groups affect protein folding. Angew Chem Int Ed 45:4198–4203

    Article  Google Scholar 

  • Kaiser E, Colescott RL, Bossinger CD, Cook PI (1970) Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem 34:595–598

    Article  CAS  PubMed  Google Scholar 

  • Kubyshkin VS, Komarov IV, Afonin S, Mikhailiuk PK, Grage SL, Ulrich AS (2010) Trifluoromethyl-substituted α-amino acids as solid state 19F NMR labels for structural analysis of membrane-bound peptides. In: Gouverneur V, Müller K (eds) Fluorine in pharmaceutical and medicinal chemistry: from biophysical aspects to clinical applications. Imperial College Press (in print)

  • Marsh ENG, Buer BC, Ramamoorthy A (2009) Fluorine—a new element in the design of membrane-active peptides. Mol BioSyst 5:1143–1147

    Article  CAS  PubMed  Google Scholar 

  • Mason JM, Arndt KM (2004) Coiled-coil domains: stability, specificity, and biological implications. ChemBioChem 5:170–176

    Article  CAS  PubMed  Google Scholar 

  • Mikhailiuk PK, Afonin S, Chernega AN, Rusanov EB, Platonov MO, Dubinina GG, Berditsch M, Ulrich AS, Komarov IV (2006) Conformationally rigid trifluoromethyl-substituted α-amino acid designed for peptide structure analysis by solid-state 19F NMR spectroscopy. Angew Chem Int Ed 45:5659–5661

    Article  CAS  Google Scholar 

  • Mikhailiuk PK, Afonin S, Palamarchuk GV, Shishkin OV, Ulrich AS, Komarov IV (2008) Synthesis of trifluoromethyl-substituted proline analogues as 19F NMR labels for peptides in the polyproline II conformation. Angew Chem Int Ed 47:5765–5767

    Article  Google Scholar 

  • Mikhailiuk PK, Voievoda NM, Afonin S, Ulrich AS, Komarov IV (2010) An optimized protocol for the multigram synthesis of 3-(trifluoromethyl)bicyclo[1.1.1]pent-1-ylglycine (CF3-Bpg). J Fluorine Chem 131:217–220

    Article  Google Scholar 

  • Pagel K, Seeger K, Seiwert B, Villa A, Mark AE, Berger S, Koksch B (2005) Advanced approaches for the characterization of a de novo designed antiparallel coiled-coil peptide. Org Biomol Chem 3:1189–1194

    Article  CAS  PubMed  Google Scholar 

  • Salwiczek M, Samsonov S, Vagt T, Nyakatura E, Fleige E, Numata J, Cölfen H, Pisabarro MT, Koksch B (2009) Position-dependent effects of fluorinated amino acids on the hydrophobic core formation of a heterodimeric coiled coil. Chem Eur J 15:7628–7636

    Article  CAS  Google Scholar 

  • Samsonov SA, Salwiczek M, Anders G, Koksch B, Pisabarro MT (2009) Fluorine in protein environments: a QM and MD study. J Phys Chem B 113:16400–16408

    Article  CAS  PubMed  Google Scholar 

  • Sternberg U, Klipfel M, Grage SL, Witter R, Ulrich AS (2009) Calculation of fluorine chemical shift tensors for the interpretation of oriented 19F NMR spectra of gramicidin A in membranes. Phys Chem Chem Phys 11:7048–7060

    Article  CAS  PubMed  Google Scholar 

  • Strandberg E, Tremouilhac P, Wadhwani P, Ulrich AS (2009) Synergistic transmembrane insertion of the heterodimeric PGLa/magainin 2 complex studied by solid-state NMR. Biochim Biophys Acta 1788:1667–1679

    Article  CAS  PubMed  Google Scholar 

  • Tripet B, Wagschal K, Lavigne P, Mant CT, Hodges RS (2000) Effects of side-chain characteristics on stability and oligomerization state of a de novo-designed model coiled coil: 20 amino acid substitutions in position “d”. J Mol Biol 300:377–402

    Article  CAS  PubMed  Google Scholar 

  • Ulrich AS (2005) Solid state 19F NMR methods for studying biomembranes. Prog Nucl Magn Reson Spectrosc 46:1–21

    Article  CAS  Google Scholar 

  • Wadhwani P, Bürck J, Strandberg E, Mink C, Afonin S, Ulrich AS (2008) Using a sterically restrictive amino acid as a 19F NMR label to monitor and to control peptide aggregation in membranes. J Am Chem Soc 130:16515–16517

    Article  CAS  PubMed  Google Scholar 

  • Wagschal K, Tripet B, Lavigne P, Mant C, Hodges RS (1999) The role of position a in determining the stability and oligomerization state of α-helical coiled coils: 20 amino acid stability coefficients in the hydrophobic core of proteins. Protein Sci 8:2312–2329

    Article  CAS  PubMed  Google Scholar 

  • Yoder NC, Kumar K (2002) Fluorinated amino acids in protein design and engineering. Chem Soc Rev 31:335–341

    Article  CAS  PubMed  Google Scholar 

  • Zhao YH, Abraham MH, Zissimos AM (2003) Fast calculation of van der Waals volume as a sum of atomic and bond contributions and its application to drug compounds. J Org Chem 68:7368–7373

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by Deutsche Forschungsgemeinschaft (KO 1976/2-2). We are furthermore grateful to Allison Berger for proofreading of the manuscript.

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Authors and Affiliations

  1. Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany

    Mario Salwiczek & Beate Koksch

  2. Department of Chemistry, Kyiv National Taras Shevchenko University, Volodymyrska 64, Kiev, 01033, Ukraine

    Pavel K. Mikhailiuk & Igor V. Komarov

  3. Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG2) and Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany

    Sergii Afonin & Anne S. Ulrich

Authors
  1. Mario Salwiczek
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  2. Pavel K. Mikhailiuk
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  3. Sergii Afonin
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  4. Igor V. Komarov
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  5. Anne S. Ulrich
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  6. Beate Koksch
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Correspondence to Beate Koksch.

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Salwiczek, M., Mikhailiuk, P.K., Afonin, S. et al. Compatibility of the conformationally rigid CF3-Bpg side chain with the hydrophobic coiled-coil interface. Amino Acids 39, 1589–1593 (2010). https://doi.org/10.1007/s00726-010-0581-8

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  • DOI: https://doi.org/10.1007/s00726-010-0581-8

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