title: β- and γ-Amino Acids at α-Helical Interfaces: Toward the Formation of Highly Stable Foldameric Coiled Coils.
abstract: Since peptides are vital for cellular and pathogenic processes, much effort has been put into the design of unnatural oligomers that mimic natural peptide structures, also referred to as foldamers. However, to enable the specific application of foldamers, a thorough characterization of their interaction profiles in native protein environments is required. We report here the application of phage display for the identification of suitable helical environments for a sequence comprising an alternating set of β- and γ-amino acids. In vitro selected sequences show that an increase in the hydrophobic surface area at the helical interface as well as the incorporation of a polar H-bond donor functionality can significantly improve interhelical interactions involving backbone-extended amino acids. Thus, our data provide insight into the principles of the rational design of foldameric inhibitors for protein-protein interactions.
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors.forename: Elisabeth K
authors.initials: EK
authors.lastname: Nyakatura
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany ; Institute of Pharmacy, Freie Universität Berlin , Königin-Luisestrasse 2 + 4, 14194 Berlin, Germany.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Mortier
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Radtke
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wieczorek
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Rezaei Araghi
authors.affiliation: Fritz Haber Institute , Faradayweg 4-6, 14195 Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Baldauf
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin , Königin-Luisestrasse 2 + 4, 14194 Berlin, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Koksch
keywords: Phage display; chimeric peptides; βγ amino acids