000084690 001__ 84690 000084690 005__ 20200716101511.0 000084690 0247_ $$2doi$$a10.1007/s00216-018-1433-8 000084690 0248_ $$2sideral$$a109082 000084690 037__ $$aART-2019-109082 000084690 041__ $$aeng 000084690 100__ $$0(orcid)0000-0002-8839-6796$$aMahía, A.$$uUniversidad de Zaragoza 000084690 245__ $$aA 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 000084690 260__ $$c2019 000084690 5060_ $$aAccess copy available to the general public$$fUnrestricted 000084690 5203_ $$aAmyloid 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. 000084690 536__ $$9info:eu-repo/grantAgreement/ES/CI2017-001-3$$9info:eu-repo/grantAgreement/ES/DGA/E102$$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MINECO/BIO2014-53530-R$$9info:eu-repo/grantAgreement/ES/MINECO/BIO2016-783-78310-R 000084690 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000084690 590__ $$a3.637$$b2019 000084690 591__ $$aCHEMISTRY, ANALYTICAL$$b18 / 86 = 0.209$$c2019$$dQ1$$eT1 000084690 591__ $$aBIOCHEMICAL RESEARCH METHODS$$b18 / 77 = 0.234$$c2019$$dQ1$$eT1 000084690 592__ $$a0.874$$b2019 000084690 593__ $$aAnalytical Chemistry$$c2019$$dQ1 000084690 593__ $$aBiochemistry$$c2019$$dQ2 000084690 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000084690 700__ $$0(orcid)0000-0003-4358-9110$$aConde-Giménez, M. 000084690 700__ $$0(orcid)0000-0003-0195-5434$$aSalillas, S.$$uUniversidad de Zaragoza 000084690 700__ $$aPallarés, I. 000084690 700__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos, J.J.$$uUniversidad de Zaragoza 000084690 700__ $$aLasa, Í. 000084690 700__ $$aVentura, S. 000084690 700__ $$0(orcid)0000-0001-9033-8459$$aDíaz de Villegas, M.D. 000084690 700__ $$0(orcid)0000-0002-4972-7476$$aGálvez, J.A.$$uUniversidad de Zaragoza 000084690 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, J.$$uUniversidad de Zaragoza 000084690 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica 000084690 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000084690 773__ $$g411, 1 (2019), 251-265$$pAnal. Bioanal. Chem.$$tAnalytical and Bioanalytical Chemistry$$x1618-2642 000084690 8564_ $$s1902101$$uhttps://zaguan.unizar.es/record/84690/files/texto_completo.pdf$$yPostprint 000084690 8564_ $$s53247$$uhttps://zaguan.unizar.es/record/84690/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000084690 909CO $$ooai:zaguan.unizar.es:84690$$particulos$$pdriver 000084690 951__ $$a2020-07-16-09:18:44 000084690 980__ $$aARTICLE