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 alpha-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 beta-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.

A single-residue substitution inhibits fibrillization of Ala-based pentapeptides. A spectroscopic and molecular dynamics investigation / Caruso, M.; Gatto, E.; Placidi, E.; Ballano, G.; Formaggio, F.; Toniolo, C.; Zanuy, D.; Aleman, C.; Venanzi, M.. - In: SOFT MATTER. - ISSN 1744-683X. - 10:15(2014), pp. 2508-2519. [10.1039/c3sm52831f]

A single-residue substitution inhibits fibrillization of Ala-based pentapeptides. A spectroscopic and molecular dynamics investigation

Placidi E.;
2014

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 alpha-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 beta-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.
2014
Alanine; Hydrogen Bonding; Methanol; Microscopy, Atomic Force; Peptides; Protein Structure, Secondary; Water; Molecular Dynamics Simulation
01 Pubblicazione su rivista::01a Articolo in rivista
A single-residue substitution inhibits fibrillization of Ala-based pentapeptides. A spectroscopic and molecular dynamics investigation / Caruso, M.; Gatto, E.; Placidi, E.; Ballano, G.; Formaggio, F.; Toniolo, C.; Zanuy, D.; Aleman, C.; Venanzi, M.. - In: SOFT MATTER. - ISSN 1744-683X. - 10:15(2014), pp. 2508-2519. [10.1039/c3sm52831f]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1326606
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