title: Helix Nucleation by the Smallest Known α-Helix in Water.
abstract: Cyclic pentapeptides (e.g. Ac-(cyclo-1,5)-[KAXAD]-NH2 ; X=Ala, 1; Arg, 2) in water adopt one α-helical turn defined by three hydrogen bonds. NMR structure analysis reveals a slight distortion from α-helicity at the C-terminal aspartate caused by torsional restraints imposed by the K(i)-D(i+4) lactam bridge. To investigate this effect on helix nucleation, the more water-soluble 2 was appended to N-, C-, or both termini of a palindromic peptide ARAARAARA (≤5 % helicity), resulting in 67, 92, or 100 % relative α-helicity, as calculated from CD spectra. From the C-terminus of peptides, 2 can nucleate at least six α-helical turns. From the N-terminus, imperfect alignment of the Asp5 backbone amide in 2 reduces helix nucleation, but is corrected by a second unit of 2 separated by 0-9 residues from the first. These cyclic peptides are extremely versatile helix nucleators that can be placed anywhere in 5-25 residue peptides, which correspond to most helix lengths in protein-protein interactions.
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Huy N
authors.initials: HN
authors.lastname: Hoang
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Driver
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Renée L
authors.initials: RL
authors.lastname: Beyer
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hill
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Aline
authors.initials: A
authors.lastname: D de Araujo
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Fabien
authors.initials: F
authors.lastname: Plisson
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Rosemary S
authors.initials: RS
authors.lastname: Harrison
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Lena
authors.initials: L
authors.lastname: Goedecke
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. n.shepherd@imb.uq.edu.au.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Shepherd
authors.affiliation: Division of Chemistry and Structural Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. d.fairlie@imb.uq.edu.au.
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
keywords: NMR spectroscopy; circular dichroism; cyclic peptides; helical structures; helix nucleation