Design and synthesis of epicocconone analogues with improved fluorescence properties

Philippe A. Peixoto, Agathe Boulangé, Malcolm Ball, Bertrand Naudin, Thibault Alle, Pascal Cosette, Peter Karuso*, Xavier Franck

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)15248-15256
    Number of pages9
    JournalJournal of the American Chemical Society
    Volume136
    Issue number43
    DOIs
    Publication statusPublished - 29 Oct 2014

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