title: Heavy-Atom Labeled Transmembrane β-Peptides: Synthesis, CD-Spectroscopy, and X-ray Diffraction Studies in Model Lipid Multilayer.
abstract: Transmembrane β-peptides are promising candidates for the design of well-controlled membrane anchors in lipid membranes. Here, we present the synthesis of transmembrane β-peptides with and without tryptophan anchors, as well as a novel iodine-labeled d-β(3) -amino acid. By using one or more of the heavy-atom labeled amino acids as markers, the orientation of the helical peptide was inferred based on the electron-density profile determined by X-ray reflectivity. The β-peptides were synthesized through manual Fmoc-based solid-phase peptide synthesis (SPPS) and reconstituted in unilamellar vesicles forming a right-handed 314 -helix secondary structure, as shown by circular dichroism spectroscopy. We then integrated the β-peptide into solid-supported membrane stacks and carried out X-ray reflectivity and grazing incidence small-angle X-ray scattering to determine the β-peptide orientation and its effect on the membrane bilayers. These β-peptides adopt a well-ordered transmembrane motif in the solid-supported model membrane, maintaining the basic structure of the original bilayer with some distinct alterations. Notably, the helical tilt angle, which accommodates the positive hydrophobic mismatch, induces a tilt of the acyl chains. The tilted chains, in turn, lead to a membrane thinning effect.
authors.affiliation: Institute for Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Rost
authors.affiliation: Institute for X-ray Physics, Georg-August-University Göttingen, Friedrich-Hund-Platz 1, 37077, Göttingen, Germany.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute for X-ray Physics, Georg-August-University Göttingen, Friedrich-Hund-Platz 1, 37077, Göttingen, Germany. tsaldit@gwdg.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Salditt
authors.affiliation: Institute for Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077, Göttingen, Germany. udieder@gwdg.de.
authors.forename: Ulf
authors.identifier: http://orcid.org/0000-0002-2654-9160
authors.initials: U
authors.lastname: Diederichsen
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D014961:X-Ray Diffraction
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D008055:Lipids
keywords: X-ray diffraction; circular dichroism; membrane proteins; membranes; β-peptides