Orto methylated 3-hydroxypyridines hinder hen egg-white lysozyme fibrillization

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dc.contributor.author Pauwels, Kris
dc.contributor.author Casasnovas Perera, Rodrigo
dc.contributor.author Sanchís Cortés, María del Pilar
dc.contributor.author Vilanova Canet, Bartolomé
dc.contributor.author Muñoz Izquierdo, Francisco
dc.contributor.author Donoso Pardo, Josefa Laurentina
dc.contributor.author Adrover Estelrich, Miguel
dc.date.accessioned 2018-10-30T13:08:03Z
dc.identifier.uri http://hdl.handle.net/11201/148331
dc.description.abstract [eng] Protein aggregation with the concomitant formation of amyloid fibrils is related to several neurodegenerative diseases, but also to non-neuropathic amyloidogenic diseases and nonneurophatic systemic amyloidosis. Lysozyme is the protein involved in the latter, and it is widely used as a model system to study the mechanisms underlying fibril formation and its inhibition. Several phenolic compounds have been reported as inhibitors of fibril formation. However, the anti-aggregating capacity of other heteroaromatic compounds has not been studied in any depth. We have screened the capacity of eleven different hydroxypyridines to affect the acid-induced fibrillization of hen lysozyme. Although most of the tested hydroxypyridines alter the fibrillation kinetics of HEWL, only 3-hydroxy-2-methylpyridine, 3-hydroxy-6-methylpyridine and 3-hydroxy-2,6-dimethylpyridine completely abolish fibril formation. Different biophysical techniques and several theoretical approaches are combined to elucidate their mechanism of action. O-methylated 3-hydroxypyridines bind non-cooperatively to two distinct but amyloidogenic regions of monomeric lysozyme. This stabilises the protein structure, as evidenced by enhanced thermal stability, and results in the inhibition of the conformational transition that precedes fibril assembly. Our results point to o-methylated 3-hydroxypyridines as a promising molecular scaffold for the future development of novel fibrillization inhibitors. Many proteins, of diverse structure and function, can self-assemble into morphologically similar fibrillar
dc.format application/pdf
dc.relation.isformatof Reproducció del document publicat a: https://doi.org/10.1038/srep12052
dc.relation.ispartof Scientific Reports, 2015, vol. 5, num. 12052
dc.rights cc-by (c) Pauwels, Kris et al., 2015
dc.rights.uri http://creativecommons.org/licenses/by/3.0/es
dc.subject.classification 54 - Química
dc.subject.other 54 - Chemistry. Crystallography. Mineralogy
dc.title Orto methylated 3-hydroxypyridines hinder hen egg-white lysozyme fibrillization
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2018-10-30T13:08:04Z
dc.subject.keywords lysozyme
dc.subject.keywords Nuclear magnetic resonance
dc.subject.keywords dicroismo circular
dc.subject.keywords Differential scanning calorimetry (DSC)
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.identifier.doi https://doi.org/10.1038/srep12052

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cc-by (c) Pauwels, Kris et al., 2015 Except where otherwise noted, this item's license is described as cc-by (c) Pauwels, Kris et al., 2015

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