Issue 15, 2014

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
08 Nov 2013
Accepted
09 Dec 2013
First published
12 Dec 2013

Soft Matter, 2014,10, 2508-2519

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

M. Caruso, E. Gatto, E. Placidi, G. Ballano, F. Formaggio, C. Toniolo, D. Zanuy, C. Alemán and M. Venanzi, Soft Matter, 2014, 10, 2508 DOI: 10.1039/C3SM52831F

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