Published: March 1, 2023
Fungal and bacterial pathogens causing lung infections often use lectins to mediate adhesion glycoconjugates at the surface of host tissues. Given rapid emergence resistance treatments in current use, β-propeller such as FleA from Aspergillus fumigatus, SapL1 Scedosporium apiospermum, BambL Burkholderia ambifaria have become appealing targets for design anti-adhesive molecules. In search novel cheap anti-infectious agents, we synthesized multivalent compounds that can display up 20 units fucose, natural ligand. We obtained nanomolar inhibitors are several orders magnitude stronger than their monovalent analogue according biophysical techniques (i.e., fluorescence polarization, isothermal titration calorimetry, bio-layer interferometry). The reason high affinity might be attributed a strong aggregating mechanism, which was examined by analytical ultracentrifugation. Additional structural biology, X-ray crystallography atomic force microscopy, were used try decipher binding mode towards targets. Finally, fucosylated reduce A. fumigatus spores epithelial cells when administered 1 h before or after infection human cells. For this reason, propose them promising drugs prevention treatment aspergillosis related microbial infections.
Language: Английский