title: A coiled coil with a fluorous core.
abstract: The design, synthesis, and structural characterization of a highly fluorinated peptide system based on the coiled coil region of the yeast transcription factor GCN4 is described. All four leucine residues (a position) and three valine residues (d position) were replaced by the unnatural amino acids 5,5,5-trifluoroleucine and 4,4,4-trifluorovaline, respectively. The peptide is highly alpha-helical at low micromolar concentrations as judged by circular dichroism spectra, sediments as a dimeric species in the 5-30 microM concentration range, and exhibits a dimer melting temperature that is 15 degrees C higher than a control peptide with a hydrocarbon core. Furthermore, the apparent free energy of unfolding as calculated from guanidinium hydrochloride denaturation experiments is larger by approximately 1.0 kcal/mol for the fluorinated peptide than its hydrocarbon counterpart. We conclude that additional stability is derived from sequestering the more hydrophobic trifluoromethyl groups from aqueous solvent. These studies introduce a new paradigm in the design of molecular self-assembling systems, one based on orthogonal solubility properties of liquid phases.
authors.affiliation: Department of Chemistry, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: B
authors.initials: B
authors.lastname: Bilgiçer
authors.forename: A
authors.initials: A
authors.lastname: Fichera
authors.forename: K
authors.initials: K
authors.lastname: Kumar
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004268:DNA-Binding Proteins; D005461:Fluorine / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011489:Protein Denaturation; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014461:Ultracentrifugation
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D007202:Indicators and Reagents; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D005461:Fluorine; D011494:Protein Kinases