• Cinnamide Derivatives of d -Mannose as Inhibitors of the Bacterial Virulence Factor LecB from Pseudomonas aeruginosa

      Sommer, Roman; Hauck, Dirk; Varrot, Annabelle; Wagner, Stefanie; Audfray, Aymeric; Prestel, Andreas; Möller, Heiko M.; Imberty, Anne; Titz, Alexander; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.; Chemical Biology of Carbohydrates; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS); Universitätsstrasse 10 66123 Saarbrücken Germany; Chemical Biology of Carbohydrates; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS); Universitätsstrasse 10 66123 Saarbrücken Germany; Centre de Recherche sur les Macromolécules Végétales (CERMAV-UPR5301); CNRS and Université Grenoble Alpes, BP53; 38041 Grenoble cedex 9 France; Chemical Biology of Carbohydrates; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS); Universitätsstrasse 10 66123 Saarbrücken Germany; Centre de Recherche sur les Macromolécules Végétales (CERMAV-UPR5301); CNRS and Université Grenoble Alpes, BP53; 38041 Grenoble cedex 9 France; Department of Chemistry and Graduate School Chemical Biology; University of Konstanz; 78457 Konstanz Germany; Department of Chemistry and Graduate School Chemical Biology; University of Konstanz; 78457 Konstanz Germany; Centre de Recherche sur les Macromolécules Végétales (CERMAV-UPR5301); CNRS and Université Grenoble Alpes, BP53; 38041 Grenoble cedex 9 France; Chemical Biology of Carbohydrates; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS); Universitätsstrasse 10 66123 Saarbrücken Germany (2015-12)
    • Covalent Lectin Inhibition and Application in Bacterial Biofilm Imaging.

      Wagner, Stefanie; Hauck, Dirk; Hoffmann, Michael; Sommer, Roman; Joachim, Ines; Müller, Rolf; Imberty, Anne; Varrot, Annabelle; Titz, Alexander; HIPS, Helmholtz-Institut für pharmazeutische Forchung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany. (2017-09-28)
      Biofilm formation by pathogenic bacteria is a hallmark of chronic infections. In many cases, lectins play key roles in establishing biofilms. The pathogen Pseudomonas aeruginosa often exhibiting various drug resistances employs its lectins LecA and LecB as virulence factors and biofilm building blocks. Therefore, inhibition of the function of these proteins is thought to have potential in developing "pathoblockers" preventing biofilm formation and virulence. A covalent lectin inhibitor specific to a carbohydrate binding site is described for the first time. Its application in the LecA-specific in vitro imaging of biofilms formed by P. aeruginosa is also reported.
    • Development of a competitive binding assay for the Burkholderia cenocepacia lectin BC2L-A and structure activity relationship of natural and synthetic inhibitors

      Beshr, Ghamdan; Sommer, Roman; Hauck, Dirk; Siebert, David Chan Bodin; Hofmann, Anna; Imberty, Anne; Titz, Alexander (2016)
    • O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside.

      Sommer, Roman; Hauck, Dirk; Varrot, Annabelle; Imberty, Anne; Künzler, Markus; Titz, Alexander; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland Universitätscampus E8.1, 66123 Saarbrücken, Germany. (2016)
      Selenoglycosides are used as reactive glycosyl donors in the syntheses of oligosaccharides. In addition, such heavy atom analogs of natural glycosides are useful tools for structure determination of their lectin receptors using X-ray crystallography. Some lectins, e.g., members of the tectonin family, only bind to carbohydrate epitopes with O-alkylated ring hydroxy groups. In this context, we report the first synthesis of an O-methylated selenoglycoside, specifically methyl 2-O-methyl-L-selenofucopyranoside, a ligand of the lectin tectonin-2 from the mushroom Laccaria bicolor. The synthetic route required a strategic revision and further optimization due to the intrinsic lability of alkyl selenoglycosides, in particular for the labile fucose. Here, we describe a successful synthetic access to methyl 2-O-methyl-L-selenofucopyranoside in 9 linear steps and 26% overall yield starting from allyl L-fucopyranoside.
    • The virulence factor LecB varies in clinical isolates: consequences for ligand binding and drug discovery

      Sommer, Roman; Wagner, Stefanie; Varrot, Annabelle; Nycholat, Corwin M.; Khaledi, Ariane; Häussler, Susanne; Paulson, James C.; Imberty, Anne; Titz, Alexander (2016)