title: Polymorphism of oligomers of a peptide from β-amyloid.
abstract: This contribution reports solution-phase structural studies of oligomers of a family of peptides derived from the β-amyloid peptide (Aβ). We had previously reported the X-ray crystallographic structures of the oligomers and oligomer assemblies formed in the solid state by a macrocyclic β-sheet peptide containing the Aβ(15-23) nonapeptide. In the current study, we set out to determine its assembly in aqueous solution. In the solid state, macrocyclic β-sheet peptide 1 assembles to form hydrogen-bonded dimers that further assemble in a sandwich-like fashion to form tetramers through hydrophobic interactions between the faces bearing V18 and F20. In aqueous solution, macrocyclic β-sheet peptide 1 and homologue 2a form hydrogen-bonded dimers that assemble to form tetramers through hydrophobic interactions between the faces bearing L17, F19, and A21. In the solid state, the hydrogen-bonded dimers are antiparallel, and the β-strands are fully aligned, with residues 17-23 of one of the macrocycles aligned with residues 23-17 of the other. In solution, residues 17-23 of the hydrogen-bonded dimers are shifted out of alignment by two residues toward the C-termini. The two hydrogen-bonded dimers are nearly orthogonal in the solid state, while in solution the dimers are only slightly rotated. The differing morphology of the solution-state and solid-state tetramers is significant, because it may provide a glimpse into some of the structural bases for polymorphism among Aβ oligomers in Alzheimer's disease.
authors.affiliation: Department of Chemistry, University of California, Irvine , Irvine, California 92697-2025, United States.
authors.forename: Johnny D
authors.initials: JD
authors.lastname: Pham
authors.forename: Borries
authors.initials: B
authors.lastname: Demeler
authors.forename: James S
authors.initials: JS
authors.lastname: Nowick
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D010455:Peptides