title: Controlling the morphology of cross beta-sheet assemblies by rational design.
abstract: Low molecular weight peptidomimetics with simple amphiphilic sequences can help to elucidate the structures of cross beta-sheet assemblies, such as amyloid fibrils. The peptidomimetics described herein comprise a dibenzofuran template, two peptide strands made up of alternating hydrophilic and hydrophobic residues, and carboxyl termini, each of which can be varied to probe the structural requirements for beta-sheet self-assembly processes. The dibenzofuran template positions the strands approximately 10 A apart, allowing corresponding hydrophobic side chains in the strands to pack into a collapsed U-shaped structure. This conformation is stabilized by hydrophobic interactions, not intramolecular hydrogen bonds. Intermolecular stacking of the collapsed peptidomimetics, enabled by intermolecular hydrogen bonding and hydrophobic interactions, affords 25-27 A wide protofilaments having a cross beta-sheet structure. Association of protofilaments, mediated by the dibenzofuran substructures and driven by the hydrophobic effect, affords 50-60 A wide filaments. These widths can be controlled by changing the length of the peptide strands. Further assembly of the filaments into fibrils or ribbons can be controlled by modification of the template, C-terminus, and buffer ion composition.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Songpon
authors.initials: S
authors.lastname: Deechongkit
authors.forename: Evan T
authors.initials: ET
authors.lastname: Powers
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: You
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
mesh_terms: D000577:Amides / Q000737:chemistry; D001572:Benzofurans / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D000577:Amides; D001572:Benzofurans; D010455:Peptides; D011506:Proteins; C023614:dibenzofuran