title: Design and synthesis of epicocconone analogues with improved fluorescence properties.
abstract: 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.
authors.affiliation: Normandie Université, COBRA, UMR 6014 & FR 3038; Université de Rouen; INSA Rouen; CNRS, 1 rue Tesnière, 76821 Mont-Saint-Aignan Cedex, France.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Peixoto
authors.forename: Agathe
authors.initials: A
authors.lastname: Boulangé
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ball
authors.forename: Bertrand
authors.initials: B
authors.lastname: Naudin
authors.forename: Thibault
authors.initials: T
authors.lastname: Alle
authors.forename: Pascal
authors.initials: P
authors.lastname: Cosette
authors.forename: Peter
authors.initials: P
authors.lastname: Karuso
authors.forename: Xavier
authors.initials: X
authors.lastname: Franck
mesh_terms: D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D015195:Drug Design; D004355:Drug Stability; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D001578:Benzopyrans; D005456:Fluorescent Dyes; D005663:Furans; D007659:Ketones; C477464:epicocconone