Compatibility of the conformationally rigid CF3-Bpg side chain with the hydrophobic coiled-coil interface
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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.
KeywordsFluorinated amino acids CF3-Bicyclopentyl glycine α-Helical coiled coil Solid state 19F NMR 19F labelling
This research was supported by Deutsche Forschungsgemeinschaft (KO 1976/2-2). We are furthermore grateful to Allison Berger for proofreading of the manuscript.
- 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 183–207Google 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)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 45:5659–5661CrossRefGoogle Scholar