title: Analysis of selected and designed chimeric D- and L-α-helix assemblies.
abstract: D-peptides have been attributed pharmacological advantages over regular L-peptides, yet design rules are largely unknown. Based on a designed coiled coil-like D/L heterotetramer, named L-Base/D-Acid, we generated a library offering alternative residues for interaction with the D-peptide. Phage display selection yielded one predominant peptide, named HelixA, that differed at 13 positions from the scaffold helix. In addition to the observed D-/L-heterotetramers, ratio-dependent intermediate states were detected by isothermal titration calorimetry. Importantly, the formation of the selected HelixA/D-Acid bundle passes through fewer intermediate states than L-Base/D-Acid. Back mutation of HelixA core residues to L-Base (HelixLL) revealed that the residues at e/g-positions are responsible for the different intermediates. Furthermore, a Val-core variant (PeptideVV) was completely devoid of binding D-Acid, whereas an Ile-core helix (HelixII) interacted with D-Acid in a significantly more specific complex than L-Base.
authors: Molecular Biotechnology, Institute for Biochemistry and Biology, University of Potsdam , 14476 Potsdam, Germany.
authors: Tim
authors: T
authors: Kükenshöner
authors: Urs B
authors: UB
authors: Hagemann
authors: Daniel
authors: D
authors: Wohlwend
authors: Christina
authors: C
authors: Räuber
authors: Tobias
authors: T
authors: Baumann
authors: Sandro
authors: S
authors: Keller
authors: Oliver
authors: O
authors: Einsle
authors: Kristian M
authors: KM
authors: Müller
authors: Katja M
authors: KM
authors: Arndt
mesh_terms: D019943:Amino Acid Substitution; D046912:Multiprotein Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D020125:Mutation, Missense; D019151:Peptide Library; D017433:Protein Structure, Secondary
chemical_list: D046912:Multiprotein Complexes; D019151:Peptide Library