Synthesis and thermodynamic characterization of self-sorting coiled coils

Abstract

Hydrophobic interactions are a major driving force in protein folding. Amino acid side chains containing trifluoromethyl groups are more hydrophobic than their hydrocarbon counterparts. We describe here the design and characterization of peptide systems with hydrophobic cores composed entirely of leucine or hexafluoroleucine. The preference for homodimeric assemblies over the heterodimer was probed by a disulfide exchange assay. At equilibrium, the homodimers are the dominant species in solution. The fluorinated assembly is much more stable than the hydrogenated peptide dimer and the heterodimer, as judged by thermal and chemical denaturation studies and is responsible for driving the equilibrium in favor of the homodimers. Appropriately fluorinated peptides are therefore useful in stabilizing protein folds and in mediating specific protein–protein interactions.