- Start of Action – 24/6/2005; End of Action – 23/06/2010
Multivalent ligands for cholera toxin inhibition and sensing
The present project is aimed at the synthesis of efficient and selective Cholera Toxin (CT) inhibitors to be used in clinical studies and in sensing devices. The synthesis of efficient monovalent mimics of the natural ligand, the oligosaccharides o-GM1, will be pursued. The mimics’ design will be improved using NMR spectroscopy and molecular modelling studies to determine the structural similarity (including conformations) between the newly designed molecules and GM1. Few selected mimic candidates will be modified with an anchoring group and conjugated to multivalent scaffolds such as calixarenes or dendrimers using different spacers, binding groups, valency and conformational mobility of the scaffold. The complexes between all the synthesised monovalent or multivalent ligands of CT will be structurally characterised in solution by NMR techniques and their stability evaluated using different complementary techniques such as fluorescence, SPR and ELISA tests. High-affinity ligands for CT will possibly lead to candidate drugs able to block the interaction of the toxin with the target cells, thus preventing the onset of the disease. Some of the strongest inhibitors will be also anchored on solid supports (silicon or gold) to develop sensors for Cholera Toxin. Finally new diagnostic ELISA’s tests for the direct identification of LOS-induced antibody responses in various groups of Guillain-Barré Syndrome affected patients will be developed.