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.

• MeSH
• antibakteriální látky chemie   farmakologie   terapeutické užití   MeSH
• bakteriální infekce farmakoterapie   mikrobiologie   MeSH
• bakteriální proteiny antagonisté a inhibitory   chemie   izolace a purifikace   metabolismus   MeSH
• dendrimery chemie   farmakologie   terapeutické užití   MeSH
• erytrocyty MeSH
• fukosa analogy a deriváty   farmakologie   terapeutické užití   MeSH
• hemaglutinace účinky léků   MeSH
• interakce hostitele a patogenu účinky léků   MeSH
• krystalografie rentgenová MeSH
• lektiny antagonisté a inhibitory   chemie   izolace a purifikace   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• molekulární modely MeSH
• Photorhabdus metabolismus   MeSH
• povrchová plasmonová rezonance MeSH
• rekombinantní proteiny chemie   izolace a purifikace   metabolismus   MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• bakteriální proteiny MeSH
• dendrimery MeSH
• fucose-binding lectin MeSH Prohlížeč
• fukosa MeSH
• lektiny MeSH
• ligandy MeSH
• rekombinantní proteiny MeSH