84690 20200716101511.0 doi 10.1007/s00216-018-1433-8 sideral 109082 ART-2019-109082 eng (orcid)0000-0002-8839-6796 Mahía, A. Universidad de Zaragoza A pyrene-inhibitor fluorescent probe with large Stokes shift for the staining of Aß1-42, a-synuclein, and amylin amyloid fibrils as well as amyloid-containing Staphylococcus aureus biofilms 2019 Access copy available to the general public Unrestricted Amyloid fibrils formed by a variety of peptides are biological markers of different human diseases, such as Alzheimer’s disease, Parkinson’s disease, and type II diabetes, and are structural constituents of bacterial biofilms. Novel fluorescent probes offering improved sensitivity or specificity toward that diversity of amyloid fibrils or providing alternative spectral windows are needed to improve the detection or the identification of amyloid structures. One potential source for such new probes is offered by molecules known to interact with fibrils, such as the inhibitors of amyloid aggregation found in drug discovery projects. Here we show the feasibility of the approach by designing, synthesizing, and testing several pyrene-based fluorescent derivatives of a previously discovered inhibitor of the aggregation of the Aß1–42 peptide. All the derivatives tested retain the interaction with the amyloid architecture and allow its staining. The most soluble derivative, N-acetyl-2-(2-methyl-4-oxo-5,6,7,8-tetrahydro-4H-benzo[4,5]thieno[2,3-d][1,3]oxazin-7-yl)-N-(pyren-1-ylmethyl)acetamide (compound 1D), stains similarly well amyloid fibrils formed by Aß1–42, a-synuclein, or amylin, provides a sensitivity only slightly lower than that of thioflavin T, displays a large Stokes shift, allows efficient excitation in the UV spectral region, and is not cytotoxic. Compound 1D can also stain amyloid fibrils formed by staphylococcal peptides present in biofilm matrices and can be used to distinguish, by direct staining, Staphylococcus aureus biofilms containing amyloid-forming phenol-soluble modulins from those lacking them. info:eu-repo/grantAgreement/ES/CI2017-001-3 info:eu-repo/grantAgreement/ES/DGA/E102 info:eu-repo/grantAgreement/ES/DGA/E45-17R info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P info:eu-repo/grantAgreement/ES/MINECO/BIO2014-53530-R info:eu-repo/grantAgreement/ES/MINECO/BIO2016-783-78310-R info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 3.637 2019 CHEMISTRY, ANALYTICAL 18 / 86 = 0.209 2019 Q1 T1 BIOCHEMICAL RESEARCH METHODS 18 / 77 = 0.234 2019 Q1 T1 0.874 2019 Analytical Chemistry 2019 Q1 Biochemistry 2019 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion (orcid)0000-0003-4358-9110 Conde-Giménez, M. (orcid)0000-0003-0195-5434 Salillas, S. Universidad de Zaragoza Pallarés, I. (orcid)0000-0002-1896-7805 Galano-Frutos, J.J. Universidad de Zaragoza Lasa, Í. Ventura, S. (orcid)0000-0001-9033-8459 Díaz de Villegas, M.D. (orcid)0000-0002-4972-7476 Gálvez, J.A. Universidad de Zaragoza (orcid)0000-0002-2879-9200 Sancho, J. Universidad de Zaragoza 2013 765 Universidad de Zaragoza Dpto. Química Orgánica Área Química Orgánica 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 411, 1 (2019), 251-265 Anal. Bioanal. Chem. Analytical and Bioanalytical Chemistry 1618-2642 1902101 http://zaguan.unizar.es/record/84690/files/texto_completo.pdf Postprint 53247 http://zaguan.unizar.es/record/84690/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:84690 articulos driver 2020-07-16-09:18:44 ARTICLE