Ortho-methylated 3-hydroxypyridines hinder hen egg-white lysozyme fibrillogenesis

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dc.contributor.author Mariño, Laura
dc.contributor.author Pauwels, Kris
dc.contributor.author Casasnovas, Rodrigo
dc.contributor.author Sanchis, Pilar
dc.contributor.author Vilanova Canet, Bartolomé
dc.contributor.author Muñoz Izquierdo, Francisco
dc.contributor.author Donoso, Josefa
dc.contributor.author Adrover Estelrich, Miguel
dc.date.accessioned 2015-09-22T12:03:11Z
dc.date.available 2015-09-22T12:03:11Z
dc.date.issued 2015-07-14
dc.identifier.citation 2045-2322
dc.identifier.uri http://hdl.handle.net/11201/1486
dc.description.abstract 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
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.isformatof Reproducció del document publicat a: http://www.nature.com/srep/2015/150714/srep12052/full/srep12052.html
dc.relation.ispartof Scientific Reports, 2015, vol. 5, num. 12052, p. 1-14
dc.rights cc-by (c) Mariño, Laura et al., 2015
dc.rights.uri http://creativecommons.org/licenses/by/3.0/es
dc.subject.classification Matèries generals UIB::Química ca
dc.title Ortho-methylated 3-hydroxypyridines hinder hen egg-white lysozyme fibrillogenesis
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2015-09-22T12:03:12Z
dc.rights.accessRights info:eu-repo/semantics/openAccess

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

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