Publication details

Synthesis of a-L-fucopyranoside-presenting glycoclusters and investigation of their interaction with recombinant Photorhabdus asymbiotica lectin (PHL)

Authors

JANČAŘÍKOVÁ Gita HERCZEG Mihály FUJDIAROVÁ Eva HOUSER Josef KÖVÉR Katalin E. BORBÁS Anikó WIMMEROVÁ Michaela CSÁVÁS Magdolna

Year of publication 2018
Type Article in Periodical
Magazine / Source Chemistry - A European Journal
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://onlinelibrary.wiley.com/doi/10.1002/chem.201705853/full
Doi http://dx.doi.org/10.1002/chem.201705853
Field Biochemistry
Keywords fucoclusters; lectin; multivalency; Photorhabdus asymbiotica; agglutination
Description 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, a-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 a-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 a-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.
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