COMBINATORIAL SURFACES MIMICKING HEPARAN SULFATE BIOLOGICAL ACTIVITIES: UNEXPECTED APPLICATION TO NEW ELECTRONIC TONGUE DEVICES

David Bonnaffé 3 Yanxia Hou-Broutin 1 Maria Genua 1 Arnaud Buhot 1 Hugues Lortat-Jacob 2 Thierry Livache 1
1INAC/CEA, SPrAM, UMR 5819, Grenoble
2CEA-CNRS-UJF-Grenoble 1, Institut de Biologie Structurale, UMR 5075, Grenoble
3Institut de Chimie Moléculaire et des Matériaux d'Orsay, UMR 8182, LabEx LERMIT, University of Paris Sud, Orsay

Heparan Sulphate (HS) is a linear and sulfated polysaccharide, displaying one of the highest information content amongst all biopolymers. Its biosynthesis, allows generating different epimerisation and sulfation patterns, with the presumed aim of promoting selective interactions with HS binding proteins (HSBPs). In order to elucidate the structural determinants allowing tight and specific binding of an HS fragment to an HSBP of therapeutic interest, total synthesis proved to be an invaluable tool.[1] However, HS fragment synthesis is notoriously difficult and the syntheses of mimetics brought interesting breakthrough for future therapeutics.[2] Going further, we reasoned that increased efficiency in such structure activity relationship studies could be gained if oligosaccharide synthesis was replaced by self assembly processes. We will show here that different 2D combinatorial surfaces, generated by the self-assembly of different controlled mixtures of disaccharide building blocks, can distinguish different HSBPs. Interestingly, we found that such combinatorial 2D surfaces could be arranged to form a cross correlated receptor network and integrated as new detection system in new electronic tongue devices.[3]

References:

1. M. Petitou, C. A. A. van Boeckel, Angew. Chem., Int. Ed. 2004, 43, 3118. F. Baleux, L. Loureiro-Morais, Y. Hersant, P. Clayette, F. Arenzana-Seisdedos, D. Bonnaffé, H. Lortat-Jacob. Nature Chemical Biology 2009, 5 (10), 743-748. D. Bonnaffé. C. R. Chimie 2011, 14, 29-73.

2. A. Lubineau, H. Lortat-Jacob, O. Gavard, S. Sarrazin, D. Bonnaffé, Chem. Eur.J. 2004, 10, 4265-4282. Connell, B. J.; Baleux, F.; Coïc, Y-M.; Clayette, P.; Bonnaffé, D.; Lortat-Jacob, H. Chemistry and Biology, 2012, 19, 131-139.

3. Y. Hou, M. Genua, D. Tada Batista, R. Calemczuk, A. Buhot, P. Fornarelli, J. Koubachi, D. Bonnaffé, E. Saesen, C. Laguri, H. Lortat-Jacob, T. Livache, Angew. Chem. 2012, 51, 10394-10398.








 




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