Fucosylated inhibitors of recently identified bangle lectin from Photorhabdus asymbiotica

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Authors

PAULÍKOVÁ Gita HOUSER Josef KASAKOVA Martina OROSZOVA Beata BERTOLOTTI Benedetta PARKAN Kamil MORAVCOVÁ Jitka WIMMEROVÁ Michaela

Year of publication 2019
Type Article in Periodical
Magazine / Source Scientific reports
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://www.nature.com/articles/s41598-019-51357-9.pdf
Doi http://dx.doi.org/10.1038/s41598-019-51357-9
Keywords lectin PHL; inhibitor; fucose
Description A recently described bangle lectin (PHL) from the bacterium Photorhabdus asymbiotica was identified as a mainly fucose- binding protein that could play an important role in the host-pathogen interaction and in the modulation of host immune response. Structural studies showed that PHL is a homo-dimer that contains up to seven L-fucose-specific binding sites per monomer. For these reasons, potential ligands of the PHL lectin: alpha-L-fucopyranosyl-containing mono-, di-, tetra-, hexa- and dodecavalent ligands were tested. Two types of polyvalent structures were investigated -calix[4]arenes and dendrimers. The shared feature of all these structures was a C-glycosidic bond instead of the more common but physiologically unstable O-glycosidic bond. The inhibition potential of the tested structures was assessed using different techniques - hemagglutination, surface plasmon resonance, isothermal titration calorimetry, and cell cross-linking. All the ligands proved to be better than free L-fucose. The most active hexava lent dendrimer exhibited affinity three orders of magnitude higher than that of standard L-fucose. To determine the binding mode of some ligands, crystal complex PHL/fucosides 2 -4 were prepared and studied using X-ray crystallography. The electron density in complexes proved the presence of the compounds in 6 out of 7 fucose-binding sites.
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