Design and Synthesis of Epicocconone Analogues with Improved Fluorescence Properties
| Autor: | Peter Karuso, Xavier Franck, Bertrand Naudin, Philippe A. Peixoto, Malcolm S. Ball, Thibault Alle, Pascal Cosette, Agathe Boulangé |
|---|---|
| Přispěvatelé: | Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Fluorophore
Epicocconone Chemistry Techniques Synthetic [CHIM.THER]Chemical Sciences/Medicinal Chemistry Ring (chemistry) Biochemistry Catalysis symbols.namesake chemistry.chemical_compound Colloid and Surface Chemistry Drug Stability [CHIM.ANAL]Chemical Sciences/Analytical chemistry Stokes shift Organic chemistry Benzopyrans Furans ComputingMilieux_MISCELLANEOUS Fluorescent Dyes Detection limit Natural product Chemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry Total synthesis General Chemistry [CHIM.CATA]Chemical Sciences/Catalysis Ketones Combinatorial chemistry Fluorescence [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry Spectrometry Fluorescence Cyclization Drug Design symbols Thermodynamics [CHIM.CHEM]Chemical Sciences/Cheminformatics |
| Zdroj: | Journal of the American Chemical Society Journal of the American Chemical Society, American Chemical Society, 2014, 136 (43), pp.15248-15256. ⟨10.1021/ja506914p⟩ |
| ISSN: | 0002-7863 1520-5126 |
| DOI: | 10.1021/ja506914p⟩ |
| Popis: | Epicocconone is a natural latent fluorophore that is widely used in biotechnology because of its large Stokes shift and lack of fluorescence in its unconjugated state. However, the low photostability and quantum yields of epicocconone have limited its wider use, and in the absence of a total synthesis, this limitation has been a long-standing problem. Here we report a general strategy for the synthesis of epicocconone analogues that relies on a 2-iodoxybenzoic acid-mediated dearomatization and on the replacement of the triene tail of the natural product by an aromatic ring. This design element is general and the synthesis is straightforward, providing ready access to libraries of polyfunctional fluorophores with long Stokes shifts based on the epicocconone core. Our structural modifications resulted in analogues with increased photostability and quantum yields compared with the natural product. Staining proteomic gels with these new analogues showed significant lowering of the detection limit and a 30% increase in the number of low-abundance proteins detected. These epiccoconone analogues will substantially improve the discovery rate of biomarker needles in the proteomic haystack. |
| Databáze: | OpenAIRE |
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