title: A single-residue substitution inhibits fibrillization of Ala-based pentapeptides. A spectroscopic and molecular dynamics investigation.
abstract: The aggregation properties of two Ala-based pentapeptides were investigated by spectroscopic techniques and molecular dynamics (MD) simulations. The two peptides, both functionalized at the N-terminus with a pyrenyl group, differ in the insertion of an α-aminoisobutyric acid residue at position 4. We showed that this single modification of the homo-peptide sequence inhibits the aggregation of the pentapeptide in aqueous solutions. Atomic force microscopy imaging revealed that the two peptides form mesoscopic aggregates of very different morphologies when deposited on mica. MD experiments showed that the two peptides have a very different propensity to form β-pleated sheet structures, as confirmed by our spectroscopic measurements. The implications of these findings for our understanding of the mechanism leading to the formation of amyloid structures, primary responsible for numerous neurodegenerative diseases, are also discussed.
authors.affiliation: Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", 00133 Rome, Italy. venanzi@uniroma2.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Caruso
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gatto
authors.forename: Ernesto
authors.initials: E
authors.lastname: Placidi
authors.forename: Gema
authors.initials: G
authors.lastname: Ballano
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
authors.forename: David
authors.initials: D
authors.lastname: Zanuy
authors.forename: Carlos
authors.initials: C
authors.lastname: Alemán
authors.forename: Mariano
authors.initials: M
authors.lastname: Venanzi
mesh_terms: D000409:Alanine / Q000737:chemistry*; D006860:Hydrogen Bonding; D000432:Methanol / Q000737:chemistry; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D014867:Water; D000409:Alanine; D000432:Methanol