» This project aims to antagonize for the first time the superlectin BC2L-C from multi-drug resistant (MDR) pathogen Burkholderia cenocepacia.
MDRs such as Burkholderia cenocepacia have become a hazard in the context of healthcare associated infections, especially for patients admitted with cystic fibrosis or immuno-compromising conditions. As other opportunistic Gram-negative bacteria, this pathogen establishes virulence and biofilms through lectin-mediated adhesion. In particular, the superlectin BC2L-C is believed to cross-link human epithelial cells to B. cenocepacia during pulmonary infection.
With the ultimate goal of inhibiting the interactions between the N-terminal of BC2L-C and its target human oligosaccharides, we aim to design glycomimetic antagonists. Here we report the structural study of the target BC2L-C-N-terminal by X-ray crystallography, followed by the design and synthesis of a modular fucoside library of C- and N-glycomimetics. Lastly, we report the biophysical evaluation of the generated glycomimetics against BC2L-CNter by techniques such as STD-NMR, SPR, ITC, DSC; resulting in a lead structure with satisfactory affinity and two crystal structures of antagonist/lectin complexes. «