Analogues of a luciferin of marine origin, few chemistry contributions
Résumé
The ever-increasing use of bioluminescence-based reporting systems led us to design a synthetic pathway amenable to gram scale preparation of stabilized O-acetylated analogues of the marine luciferin coelenterazine. [1] This provided large amounts of the O-acetyl derivatives of coelenterazine (hikarazine-086) or furimazine (hikarazine-001) [2] and an extensive structure-bioluminescence relationship study [3] using the greatly improved [4] luciferase nanoKAZ/NanoLuc led, out of 160 analogues, to the enhanced substrates hikarazine-103 or hikarazine-108. The kinetic parameters for the enzymatic reaction were also determined and provided unexpected insights on the luciferase efficacy and fragility. Further work led us to try to shift the light emission of these blue-hued luciferins. Accordingly, the even more altered analogues 1-5 were prepared and their chemiluminescence investigated. [5,6]
References
[1]E. P. Coutant, Y. L. Janin, Chem. Eur. J. 21 (2015) 17158.
[2]E. P. Coutant, S. Goyard, V. O. Hervin, G. Gagnot, R. Baatallah, T. Rose, Y. Jacob, Y. L. Janin, Org. Biomol. Chem. 17 (2019) 3709.
[3]E. P. Coutant, G. Gagnot, V. O. Hervin, R. Baatallah, S. Goyard, Y. Jacob, T. Rose, Y. L. Janin, Chem. Eur. J. 26 (2020) 948.
[4]M. P. Hall, J. Unch, B. F. Binkowski, M. P. Valley, B. L. Butler, M. G. Wood, P. Otto, K. Zimmerman, G. Vidugiris, T. Machleidt, M. B. Robers, H. A. Benink, C. T. Eggers, M. R. Slater, P. L. Meisenheimer, D. H. Klaubert, F. Fan, L. P. Encell, K. V. Wood, ACS Chem. Biol. 7 (2012) 1848.
[5]G. Gagnot, V. Hervin, E. P. Coutant, S. Goyard, Y. Jacob, T. Rose, F. E. Hibti, A. Quatela, Y. L. Janin, Chem. Eur. J. 27 (2021) 2112.
[6]G. Gagnot, P. Legrand, A. Tadros, F. E. Hibti, A. Quatela, Y. L. Janin, Synthesis 53 (2021) 2477.
Acknowledgements
Agence Nationale de la Recherche (ANR), grant ANR-11-CRNT-0004; Université Paris Descartes, Sorbonne Paris Cité; Prof. Christian Bréchot and Dr. Daniel Larzul.
Domaines
Chimie
Origine : Fichiers produits par l'(les) auteur(s)