Rafael Bermeo thesis defense on June, 18th 2021

04 June 2021
Rafael Bermeo will defend his thesis on June 18th, 2021, which he performed under the supervision of Dr. Annabelle Barrot (CNRS Research Director at Cermav - UPR5301) and which is entitled “Design, synthesis and evaluation of antagonists towards BC2L-C ”. Click on the title for more information.

Abstract:

“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.”

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