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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-64644

Waldauer, Steven A; Hassan, Shabir; Paoli, Beatrice; Donaldson, Paul M; Pfister, Rolf; Hamm, Peter; Caflisch, Amedeo; Pellarin, Riccardo (2012). Photocontrol of reversible amyloid formation with a minimal-design peptide. Journal of Physical Chemistry B, 116(30):8961-8973.

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Abstract

Amyloid aggregates are highly ordered fibrillar assemblies of polypeptides involved in a number of neurodegenerative diseases. Very little is known on the pathways of self-assembly of peptides into the final amyloid fibrils, which is due in part to the difficulty of triggering the aggregation process in a controlled manner. Here we present the design and validation of a cross-linked hexapeptide that reversibly aggregates and dissociates under ultraviolet light irradiation control. First molecular dynamics simulations were carried out to identify, among hundreds of possible sequences, those with the highest propensity to form ordered (β-sheet) oligomers in the trans state of the azobenzene cross-linker, and at the same time with the highest solubility in the cis state. In the simulations, the peptides were observed to spontaneously form ordered oligomers with cross-β contacts when the cross-linker was in the trans state, whereas in the cis state they self-assemble into amorphous aggregates. For the most promising sequence emerging from the simulations (Ac-Cys-His-Gly-Gln-Cys-Lys-NH2 cross-linked at the two cysteine residues), the photoisomerization of the azobenzene group was shown to induce reversible aggregation by time-resolved light scattering and fluorescence measurements. The amyloid-like fibrillar topology was confirmed by electron microscopy. Potential applications of minimally designed peptides with photoswitchable amyloidogenic propensity are briefly discussed.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biochemistry
07 Faculty of Science > Institute of Biochemistry

07 Faculty of Science > Institute of Physical Chemistry
DDC:570 Life sciences; biology
540 Chemistry
Language:English
Date:2012
Deposited On:19 Sep 2012 10:27
Last Modified:27 Nov 2013 23:14
Publisher:American Chemical Society
ISSN:1520-6106
Funders:Swiss National Science Foundation (SNF), ERC advanced investigator grant (DYNALLO)
Additional Information:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry B, copyright © American Chemical Society after peer review and technical editing by the publisher.
Publisher DOI:10.1021/jp305311z
PubMed ID:22724381
Citations:Web of Science®. Times Cited: 5
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