title: De novo design of a stable N-terminal helical foldamer.
abstract: A peptide NTH-18 was synthesized in which a N-terminal helix is stabilised by two crossed disulfide bonds to a C-terminal extension. The design was inspired by the structure of the neurotoxic peptide apamin, which has previously been used to stabilise helices in miniature enzymes. CD- and NMR-spectroscopy indicated that NTH-18 adopted a fold similar to that found in apamin. However, the arrangement of the elements of secondary structures was inverted relative to apamin; a N-terminal alpha-helix was connected by a reverse turn to a C-terminal extension of non-canonical secondary structure. NTH-18 displayed significant stability to heat and changes of pH. The high definition of the N-terminal end of the alpha-helix of NTH-18 should make this peptide a useful vehicle to stabilise alpha-helices in proteins with applications in protein engineering and molecular recognition.
authors.affiliation: School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Nicoll
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Weston
authors.forename: Charley
authors.initials: C
authors.lastname: Cureton
authors.forename: Christian
authors.initials: C
authors.lastname: Ludwig
authors.forename: Felican
authors.initials: F
authors.lastname: Dancea
authors.forename: Neil
authors.initials: N
authors.lastname: Spencer
authors.forename: Oliver S
authors.initials: OS
authors.lastname: Smart
authors.forename: Ulrich L
authors.initials: UL
authors.lastname: Günther
authors.forename: Rudolf K
authors.initials: RK
authors.lastname: Allemann
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D010446:Peptide Fragments