Multivalent Glycomimetics with Affinity and Selectivity toward Fucose-Binding Receptors from Emerging Pathogens.
David GoyardVeronica BaldoneschiAnnabelle VarrotMichele FioreAnne ImbertyBarbara RichichiOlivier RenaudetCristina NativiPublished in: Bioconjugate chemistry (2017)
Bacterial and fungal pathogens involved in lung infection in cystic fibrosis patients utilize a particular family of glycan-binding proteins, characterized by the presentation of six fucose-binding sites on a ring-shaped scaffold. These lectins are attractive targets for anti-infectious compounds that could interfere in the recognition of host tissues by pathogens. The design of a cyclopeptide-based hexavalent structure allowed for the presentation of six fucose residues. The synthetic hexavalent compound displays liable geometry resulting in high-avidity binding by lectins from Aspergillus fumigatus and Burkholderia ambifaria. Replacing the fucose residue with a conformationally constrained fucomimetic does not alter the affinity and provides fine specificity with no binding to other fucose-specific lectins.
Keyphrases
- cystic fibrosis
- gram negative
- end stage renal disease
- antimicrobial resistance
- ejection fraction
- newly diagnosed
- chronic kidney disease
- gene expression
- prognostic factors
- pseudomonas aeruginosa
- multidrug resistant
- case report
- dna binding
- air pollution
- patient reported outcomes
- lung function
- mass spectrometry
- capillary electrophoresis