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

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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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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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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Keywords

  • Fluorinated amino acids
  • CF3-Bicyclopentyl glycine
  • α-Helical coiled coil
  • Solid state 19F NMR
  • 19F labelling