title: Aggregation properties of the peptide fragments derived from the 17-29 region of the human and rat IAPP: a comparative study with two PEG-conjugated variants of the human sequence.
abstract: The amyloidogenic amino acid sequence Ac-VHSSNNFGAILSS-NH(2), corresponding to the 17-29 peptide region of human amylin (hIAPP17-29), was modified by grafting a hydrophilic PEG chain in order to obtain a novel class of peptides to be used as models to study the aggregation process of the full-length IAPP. The amphiphilic feature of the pegylated peptide fragment at the N-terminus (PEG-N-hIAPP17-29) drives the aggregation process toward stable micellar clusters without fibrillogenesis, despite the presence of beta-sheet interaction between peptides at pH values higher than 4.0. The hIAPP17-29-C-PEG, in which the PEG moiety is linked to the C-terminus, does not possess analogous amphiphilic character and the ability of PEG in forming H-bonds with the solvent overcomes that of the peptide chain, thereby causing peptide flocculation. The comparison with the unmodified hIAPP17-29 and the rat's peptide sequence Ac-VRSSNNLGPGLPP-NH(2)(rIAPP17-29) revealed the crucial role of hydrogen bonding between peptide and solvent in determining the aggregate structure and preventing fibril formation, as well as the non-negligible effect of a small amount of organic solvent in the aqueous solution which affects the aggregation process and rate.
authors.affiliation: CNR-Istituto per lo Studio dei Materiali Nanostrutturati, c/o Dipartimento di Chimica Inorganica, Chimica Analitica e Chimica Fisica dell'Universitá di Messina, S.ta Sperone 31, I-98166, Messina, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Mazzaglia
authors.forename: Norberto
authors.initials: N
authors.lastname: Micali
authors.forename: Luigi Monsù
authors.initials: LM
authors.lastname: Scolaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Attanasio
authors.forename: Antonio
authors.initials: A
authors.lastname: Magrí
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
authors.forename: Valentina
authors.initials: V
authors.lastname: Villari
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D006801:Humans; D006860:Hydrogen Bonding; D058228:Islet Amyloid Polypeptide; D008823:Micelles; D010446:Peptide Fragments / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D008823:Micelles; D010446:Peptide Fragments; D011092:Polyethylene Glycols