Media type: E-Article Title: Self‐assembling properties of ionic‐complementary peptides Contributor: D'Auria, Gabriella; Vacatello, Manuela; Falcigno, Lucia; Paduano, Luigi; Mangiapia, Gaetano; Calvanese, Luisa; Gambaretto, Roberta; Dettin, Monica; Paolillo, Livio imprint: Wiley, 2009 Published in: Journal of Peptide Science Language: English DOI: 10.1002/psc.1083 ISSN: 1075-2617; 1099-1387 Keywords: Organic Chemistry ; Drug Discovery ; Pharmacology ; Molecular Biology ; Molecular Medicine ; General Medicine ; Biochemistry ; Structural Biology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Self‐complementary synthetic peptides, composed by 8 and 16 residues, were analyzed by CD, NMR and small angle neutron scattering (SANS) techniques in order to investigate the relevance of charge and hydrophobic interactions in determining their self‐assembling properties. All the sequences are potentially able to form fibrils and membranes as they share, with the prototype EAK16, a strictly alternating arrangement of polar and nonpolar residues. We find that 16‐mer peptides show higher self‐assembling propensities than the 8‐mer analogs and that the aggregation processes are favored by salts and neutral pH. Peptide hydrophobic character appears as the most relevant factor in determining self‐assembling. Solution conformational analysis, diffusion and SANS measurements all together show that the sequences with a higher self‐assemble propensity are distributed, in mild conditions, between light and heavy forms. For some of the systems, the light form is mostly constituted by monomers in a random conformation, while the heavy one is constituted by β‐aggregates. In our study we also verified that sequences designed to adopt extended conformation, when dissolved in alcohol‐water mixtures, can easily fold in helix structures. In that media, the prototype of the series appears distributed between helical monomers and β‐aggregates. It is worth noticing that the structural conversion from helical monomer to β‐aggregates, mimics β‐amyloid peptide aggregation mechanisms. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.</jats:p>