Synthesis and characterization of β-peptide helices as transmembrane domains in lipid model membranes.

Aggregation, orientation and dynamics of transmembrane helices are of relevance for protein function and transmembrane signaling. To explore the interactions of transmembrane helices and the interdependence of peptide structure and lipid composition of the membranes, β-peptides were explored as model transmembrane domains. Various hydrophobic β-peptide sequences were synthesized by solid phase peptide synthesis. Conformational analyses of β-peptide helices were performed in organic solvents (methanol and 2,2,2-trifluoroethanol) and in large unilamellar liposomes (dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine and dioleoylphosphatidylcholine) indicating 12- and 14-helix conformations, depending on β -amino acid sequences. The intrinsic tryptophan fluorescence of β -homotryptophan units inserted in the center or near the end of the sequence was used to verify the membrane insertion of the β-peptides. A characteristic blue shift with peripheral β -homotryptophan compared with β-peptides with central tryptophan served as indication for a transmembrane orientation of the β-peptides within the lipid bilayer. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.