De novo design of a stable N-terminal helical foldamer.
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.
Nicoll
Andrew J
AJ
School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK.
Weston
Chris J
CJ
Cureton
Charley
C
Ludwig
Christian
C
Dancea
Felican
F
Spencer
Neil
N
Smart
Oliver S
OS
Günther
Ulrich L
UL
Allemann
Rudolf K
RK
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
D010446:Peptide Fragments