Fucosylated inhibitors of recently identified bangle lectin from Photorhabdus asymbiotica
| Autoři | |
|---|---|
| Rok publikování | 2019 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Scientific reports |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.nature.com/articles/s41598-019-51357-9.pdf |
| Doi | http://dx.doi.org/10.1038/s41598-019-51357-9 |
| Klíčová slova | lectin PHL; inhibitor; fucose |
| Popis | 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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