Photorhabdus asymbiotica is a gram-negative bacterium that is not only as effective an insect pathogen as other members of the genus, but it also causes serious diseases in humans. The recently identified lectin PHL from P. asymbiotica verifiably modulates an immune response of humans and insects, which supports the idea that the lectin might play an important role in the host-pathogen interaction. Dimeric PHL contains up to seven l-fucose-specific binding sites per monomer, and in order to target multiple binding sites of PHL, α-l-fucoside-containing di-, tri- and tetravalent glycoclusters were synthesized. Methyl gallate and pentaerythritol were chosen as multivalent scaffolds, and the fucoclusters were built from the above-mentioned cores by coupling with different oligoethylene bridges and propargyl α-l-fucosides using 1,3-dipolar azide-alkyne cycloaddition. The interaction between fucoside derivates and PHL was investigated by several biophysical and biological methods, ITC and SPR measurements, hemagglutination inhibition assay, and an investigation of bacterial aggregation properties were carried out. Moreover, details of the interaction between PHL and propargyl α-l-fucoside as a monomer unit were revealed using X-ray crystallography. Besides this, the interaction with multivalent compounds was studied by NMR techniques. The newly synthesized multivalent fucoclusters proved to be up to several orders of magnitude better ligands than the natural ligand, l-fucose.

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 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

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