Cargando…

Fucosylated inhibitors of recently identified bangle lectin from Photorhabdus asymbiotica

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Paulíková, Gita, Houser, Josef, Kašáková, Martina, Oroszová, Beáta, Bertolotti, Benedetta, Parkan, Kamil, Moravcová, Jitka, Wimmerová, Michaela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797808/
https://www.ncbi.nlm.nih.gov/pubmed/31624296
http://dx.doi.org/10.1038/s41598-019-51357-9
Descripción
Sumario: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: α-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 hexavalent 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.