Glycomimetic antagonists of mannose-specific C-lectins

Over the past few years our group has been designing and synthesizing glycomimetic molecules capable of antagonizing mannose-specific C-lectins. They were designed taking advantage of the 3D structure of known oligosaccharide ligands and of available structural information on the lectin/ligand complexes. The small-molecule monovalent ligands obtained are often endowed with limited protein affinity, but display improved drug-like properties compared to natural sugars.
This approach has allowed to identify promising mimetic leads which are giving encouraging results as antagonists of the dendritic cell lectin DC-SIGN1 and of the soluble Mannose Binding Lectin (MBL),2 recently implicated in reperfusion damage following brain stroke events. Multivalent presentation on polymeric scaffolds of these ligands has afforded high-affinity antagonists, and the selectivity of these materials against different C-lectins is being investigated.
Updates of our research will be discussed in the presentation.

[1] (a) N. Varga, I. Sutkeviciute, C. Guzzi, J. McGeagh, I. Petit-Haertlein, S. Gugliotta, J. Weiser, J. Angulo, F. Fieschi, A. Bernardi Chem. Eur. J. 2013, 19, 4786 – 4797; (b) M. Thépaut, C. Guzzi, I. Sutkeviciute, S. Sattin, R. Ribeiro-Viana, N.t Varga, E. Chabrol, J. Rojo, J. Angulo, A. Bernardi, P. M. Nieto, F. Fieschi J. Am. Chem. Soc. 2013, 135, 2518–2529
[2] F. Orsini, P. Villa, S. Parrella, R. Zangari, E. R. Zanier, R. Gesuete, M. Stravalaci, S. Fumagalli, R. Ottria, J. J. Reina, A. Paladini, E. Micotti, R. Ribeiro-Viana, J. Rojo, V. I. Pavlov, G. L. Stahl, A. Bernardi, M. Gobbi, M.G. De Simoni Circulation 2012, 126, 1484-1494