title: An unusual interstrand H-bond stabilizes the heteroassembly of helical αβγ-chimeras with natural peptides.
abstract: The substitution of α-amino acids by homologated amino acids has a strong impact on the overall structure and topology of peptides, usually leading to a loss in thermal stability. Here, we report on the identification of an ideal core packing between an α-helical peptide and an αβγ-chimera via phage display. Selected peptides assemble with the chimeric sequence with thermal stabilities that are comparable to that of the parent bundle consisting purely of α-amino acids. With the help of MD simulations and mutational analysis this stability could be explained by the formation of an interhelical H-bond between the selected cysteine and a backbone carbonyl of the β/γ-segment. Gained results can be directly applied in the design of biologically relevant peptides containing β- and γ-amino acids.
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.forename: Raheleh
authors.initials: R
authors.lastname: Rezaei Araghi
authors.forename: Jérémie
authors.initials: J
authors.lastname: Mortier
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wieczorek
authors.forename: Carsten
authors.initials: C
authors.lastname: Baldauf
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.forename: Beate
authors.initials: B
authors.lastname: Koksch
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D019151:Peptide Library; D010455:Peptides