Publication details

Fucosylated inhibitors of recently identified bangle lectin from Photorhabdus asymbiotica

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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