Chemical GAGobiology: optimized chemistry for tailored probes

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Programme Social programme Plenary speakers Keynote speakers 1st EuroCarb Young Researcher (ECYR) Workshop CarboMet Workshop Mini symposium: Glycobiology at the LUMC and beyond Favourites/Agenda

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1st EuroCarb Young Researcher (ECYR) Workshop

CarboMet Workshop

Mini symposium: Glycobiology at the LUMC and beyond

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Chemical GAGobiology: optimized chemistry for tailored probes

David Bonnaffé 1 , Christine Le Narvor 1 , Aurelien Alix 1

1 Paris Sud University, Orsay, France

Heparan Sulfate (HS), a member of the Glycosaminoglycan family, is a linear and sulfated polysaccharide displaying a high level of molecular diversity. HS chains interact and modulate the activity of numerous HS binding proteins (HSBP), amongst which validated therapeutic targets [1]. The selective inhibition of a given protein/HS interaction has been attracting increasing interest as an original therapeutic mode of action, especially since the commercialization of Arixtra® [2], the synthetic version of a pentasaccharide sequence specifically recognizing and activating antithrombin-III. To date, it has not been possible to generalize to other HSBP the strategy used to identify this sequence. In Orsay, we aim at overcoming such a bottleneck by conceiving and synthesizing tailored probes to address different aspects of HS biology and devise therapeutic innovation based on the modulation of HS-HSBP interactions [3]. To reach these aims, we developed new methodologies in organic synthesis and optimized each step by determining their critic parameters [4], thus illustrating that glycochemistry represent an ideal playground to revise central concepts in organic chemistry, as well as to initiate original developments and methodologies.

Organic synthesis for tailored probes

D. Bonnaffé. C. R. Chimie 2011, 14, 29-73. L. Kjellen, U. Lindahl. Curr. Opin. Struct. Biol. 2018, 50, 101-108.

C. A. A. van Boeckel, M. Petitou. Angew. Chem. Int. Ed. Engl. 1993, 32, 1671-1818. M. Petitou, C. A. A. van Boeckel. Angew. Chem. Int. Ed. Engl. 2004, 43, 3118-3133.

A. Lubineau, H. Lortat-Jacob, O. Gavard, S. Sarrazin, D. Bonnaffé, Chem. Eur. J. 2004, 10, 4265-4282. F. Baleux, L. Loureiro-Morais, Y. Hersant, P. Clayette, F. Arenzana-Seisdedos, D. Bonnaffé, H. Lortat-Jacob. Nature Chemical Biology 2009, 5, 743-748. K-K. Arien, F. Baleux, D.Desjardins, F. Porrot, Y-M. Coïc, J. Michiels, K. Bouchemal, D. Bonnaffé, T. Bruel, O. Schwartz, R. Le Grand, G. Vanham, N. Dereuddre-Bosquet, H. Lortat-Jacob, Scientific Reports 2016, 6, article number 34829. C. Debarnot, Y. R. Monneau, V. Roig-Zamboni, V. Delauzun, C. Le Narvor, E. Richard, J. Hénault, A. Goulet, F. Fadel, R. R. Vivès, B. Priem, D. Bonnaffé, H. Lortat-Jacob, Y. Bourne, Proc. Natl. Acad. Sci. USA 2019, 116 (14), 6760-6765.

R. Lucas, D. Hamza, A. Lubineau, D. Bonnaffé, Eur. J. Org. Chem. 2004, 2107-2117. A. Dilhas, R. Lucas, L. Loureiro-Morais, Y. Hersant, D. Bonnaffé. J. Comb. Chem. 2008, 10, 166–169. A. Bernardin, A. Cazet, L. Guyon, P. Delannoy, F. Vinet, D. Bonnaffé, I. Texier, Bioconjugate Chem. 2010, 21, 583-588. G. Povie, A-T. Tran, D. Bonnaffé, J. Habegger, Z. Hu, C. Le Narvor, P. Renaud, Angew. Chem. Int. Ed. 2014, 53, 3894–3898.

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