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Brissonnet, Yoan; Assailly, Coralie; Saumonneau, Amélie; Bouckaert, Julie; Maillasson, Mike; Petitot, Clémence; Roubinet, Benoit; Didak, Blanka; Landemarre, Ludovic; Bridot, Clarisse; Blossey, Ralf; Deniaud, David; Yan, Xibo; Bernard, Julien; Tellier, Charles; Grandjean, Cyrille; Daligault, Franck; Gouin, Sébastien G.

Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases

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  • Medientyp: E-Artikel
  • Titel: Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases
  • Beteiligte: Brissonnet, Yoan; Assailly, Coralie; Saumonneau, Amélie; Bouckaert, Julie; Maillasson, Mike; Petitot, Clémence; Roubinet, Benoit; Didak, Blanka; Landemarre, Ludovic; Bridot, Clarisse; Blossey, Ralf; Deniaud, David; Yan, Xibo; Bernard, Julien; Tellier, Charles; Grandjean, Cyrille; Daligault, Franck; Gouin, Sébastien G.
  • Erschienen: Wiley, 2019
  • Erschienen in: Chemistry – A European Journal
  • Sprache: Englisch
  • DOI: 10.1002/chem.201805790
  • ISSN: 0947-6539; 1521-3765
  • Schlagwörter: General Chemistry ; Catalysis ; Organic Chemistry
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often flanked with carbohydrate‐binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Herein, non‐hydrolyzable multivalent thiosialosides were designed as probes and inhibitors of <jats:italic>V. cholerae</jats:italic>, <jats:italic>T. cruzi</jats:italic>, and <jats:italic>S. pneumoniae</jats:italic> (<jats:italic>NanA</jats:italic>) sialidases. <jats:italic>NanA</jats:italic> was truncated from the catalytic and lectinic domains (<jats:italic>NanA‐L</jats:italic> and <jats:italic>NanA‐C</jats:italic>) to probe their respective roles upon interacting with sialylated surfaces and the synthetically designed di‐ and polymeric thiosialosides. The <jats:italic>NanA</jats:italic>‐L domain was shown to fully drive <jats:italic>NanA</jats:italic> binding, improving affinity for the thiosialylated surface and compounds by more than two orders of magnitude. Importantly, each thiosialoside grafted onto the polymer was also shown to reduce <jats:italic>NanA</jats:italic> and <jats:italic>NanA‐C</jats:italic> catalytic activity with efficiency that was 3000‐fold higher than that of the monovalent thiosialoside reference. These results extend the concept of multivalency for designing potent bacterial and parasitic sialidase inhibitors.</jats:p>