Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-β-d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis.

Central European Institute of Technology Masaryk University Kamenice 5 625 00 Brno Czech Republic

Department of Biochemistry Faculty of Science Masaryk University Kotlářská 2 611 37 Brno Czech Republic

Department of Inorganic and Analytical Chemistry University of Debrecen Egyetem tér 1 H 4032 Debrecen Hungary

Department of Organic Chemistry University of Debrecen Egyetem tér 1 H 4032 Debrecen Hungary

Department of Pharmaceutical Chemistry University of Debrecen Egyetem tér 1 H 4032 Debrecen Hungary

National Centre for Biomolecular Research Faculty of Science Masaryk University Kotlářská 2 611 37 Brno Czech Republic

Research Group for Molecular Recognition and Interaction Hungarian Academy of Sciences University of Debrecen Egyetem tér 1 H 4032 Debrecen Hungary

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Bispecific Thio-Linked Disaccharides as Inhibitors of Pseudomonas Aeruginosa Lectins LecA (PA-IL) and LecB (PA-IIL): Dual-Targeting Strategy