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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages15248-15256
Number of pages9
JournalJournal of the American Chemical Society
Volume136
Issue number43
DOIs
Publication statusPublished - 29 Oct 2014

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Fluorophores
Fluorescence
Quantum yield
Biological Products
Proteomics
Biomarkers
Biotechnology
Needles
Gels
Libraries
Proteins
Limit of Detection
Acids
Staining and Labeling
epicocconone

Cite this

Peixoto, P. A., Boulangé, A., Ball, M., Naudin, B., Alle, T., Cosette, P., ... Franck, X. (2014). Design and synthesis of epicocconone analogues with improved fluorescence properties. Journal of the American Chemical Society, 136(43), 15248-15256. https://doi.org/10.1021/ja506914p
Peixoto, Philippe A. ; Boulangé, Agathe ; Ball, Malcolm ; Naudin, Bertrand ; Alle, Thibault ; Cosette, Pascal ; Karuso, Peter ; Franck, Xavier. / Design and synthesis of epicocconone analogues with improved fluorescence properties. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 43. pp. 15248-15256.
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Peixoto, PA, Boulangé, A, Ball, M, Naudin, B, Alle, T, Cosette, P, Karuso, P & Franck, X 2014, 'Design and synthesis of epicocconone analogues with improved fluorescence properties', Journal of the American Chemical Society, vol. 136, no. 43, pp. 15248-15256. https://doi.org/10.1021/ja506914p

Design and synthesis of epicocconone analogues with improved fluorescence properties. / Peixoto, Philippe A.; Boulangé, Agathe; Ball, Malcolm; Naudin, Bertrand; Alle, Thibault; Cosette, Pascal; Karuso, Peter; Franck, Xavier.

In: Journal of the American Chemical Society, Vol. 136, No. 43, 29.10.2014, p. 15248-15256.

Research output: Contribution to journalArticleResearchpeer-review

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Peixoto PA, Boulangé A, Ball M, Naudin B, Alle T, Cosette P et al. Design and synthesis of epicocconone analogues with improved fluorescence properties. Journal of the American Chemical Society. 2014 Oct 29;136(43):15248-15256. https://doi.org/10.1021/ja506914p