dc.contributor.author | Parlato, Raffaella | |
dc.contributor.author | Volarić, Jana | |
dc.contributor.author | Lasorsa, Alessia | |
dc.contributor.author | Bagherpoor Helabad, Mahdi | |
dc.contributor.author | Kobauri, Piermichele | |
dc.contributor.author | Jain, Greeshma | |
dc.contributor.author | Miettinen, Markus | |
dc.contributor.author | Feringa, Ben L. | |
dc.contributor.author | Szymanski, Wiktor | |
dc.contributor.author | van der Wel, Patrick C. A. | |
dc.date.accessioned | 2024-08-01T08:17:10Z | |
dc.date.available | 2024-08-01T08:17:10Z | |
dc.date.created | 2024-02-01T14:43:51Z | |
dc.date.issued | 2024 | |
dc.identifier.issn | 0002-7863 | |
dc.identifier.uri | https://hdl.handle.net/11250/3143996 | |
dc.description.abstract | A family of neurodegenerative diseases, including Huntington’s disease (HD) and spinocerebellar ataxias, are associated with an abnormal polyglutamine (polyQ) expansion in mutant proteins that become prone to form amyloid-like aggregates. Prior studies have suggested a key role for β-hairpin formation as a driver of nucleation and aggregation, but direct experimental studies have been challenging. Toward such research, we set out to enable spatiotemporal control over β-hairpin formation by the introduction of a photosensitive β-turn mimic in the polypeptide backbone, consisting of a newly designed azobenzene derivative. The reported derivative overcomes the limitations of prior approaches associated with poor photochemical properties and imperfect structural compatibility with the desired β-turn structure. A new azobenzene-based β-turn mimic was designed, synthesized, and found to display improved photochemical properties, both prior and after incorporation into the backbone of a polyQ polypeptide. The two isomers of the azobenzene-polyQ peptide showed different aggregate structures of the polyQ peptide fibrils, as demonstrated by electron microscopy and solid-state NMR (ssNMR). Notably, only peptides in which the β-turn structure was stabilized (azobenzene in the cis configuration) closely reproduced the spectral fingerprints of toxic, β-hairpin-containing fibrils formed by mutant huntingtin protein fragments implicated in HD. These approaches and findings will enable better deciphering of the roles of β-hairpin structures in protein aggregation processes in HD and other amyloid-related neurodegenerative diseases. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | ACS | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Photocontrol of the β-Hairpin Polypeptide Structure through an Optimized Azobenzene-Based Amino Acid Analogue | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2024 The Author(s) | en_US |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 2 | |
dc.identifier.doi | 10.1021/jacs.3c11155 | |
dc.identifier.cristin | 2242062 | |
dc.source.journal | Journal of the American Chemical Society | en_US |
dc.source.pagenumber | 2062–2071 | en_US |
dc.identifier.citation | Journal of the American Chemical Society. 2024, 146 (3), 2062–2071 . | en_US |
dc.source.volume | 146 | en_US |
dc.source.issue | 3 | en_US |