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

Mahía, A. (Universidad de Zaragoza) ; Conde-Giménez, M. ; Salillas, S. (Universidad de Zaragoza) ; Pallarés, I. ; Galano-Frutos, J.J. (Universidad de Zaragoza) ; Lasa, Í. ; Ventura, S. ; Díaz de Villegas, M.D. ; Gálvez, J.A. (Universidad de Zaragoza) ; Sancho, J. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1007/s00216-018-1433-8

Año: 2019

Publicado en: Analytical and Bioanalytical Chemistry 411, 1 (2019), 251-265
ISSN: 1618-2642

Factor impacto JCR: 3.637 (2019)

Categ. JCR: CHEMISTRY, ANALYTICAL rank: 18 / 86 = 0.209 (2019) - Q1 - T1
Categ. JCR: BIOCHEMICAL RESEARCH METHODS rank: 18 / 77 = 0.234 (2019) - Q1 - T1

Factor impacto SCIMAGO: 0.874 - Analytical Chemistry (Q1) - Biochemistry (Q2)

Financiación: info:eu-repo/grantAgreement/ES/CI2017-001-3
Financiación: info:eu-repo/grantAgreement/ES/DGA/E102
Financiación: info:eu-repo/grantAgreement/ES/DGA/E45-17R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2014-53530-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2016-783-78310-R

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)