This work reveals new structural relationships in the complex process of the interaction between activation receptors of natural killer cells (rat NKR-P1, human CD69) and novel bivalent carbohydrate glycomimetics. The length, glycosylation pattern and linker structure of receptor ligands were examined with respect to their ability to precipitate the receptor protein from solution, which simulates the in vivo process of receptor aggregation during NK cell activation. It was found that di-LacdiNAc triazole compounds show optimal performance, reaching up to 100% precipitation of the present protein receptors, and achieving high immunostimulatory activities without any tendency to trigger activation-induced apoptosis. In the synthesis of the compounds tested, two enzymatic approaches were applied. Whereas a β-N-acetylhexosaminidase could only glycosylate one of the two acceptor sites available with yields below 10%, the Y284L mutant of human placental β1,4-galactosyltransferase-1 worked as a perfect synthetic tool, accomplishing even quantitative glycosylation at both acceptor sites and with absolute regioselectivity for the C-4 position. This work insinuates new directions for further ligand structure optimisation and demonstrates the strong synthetic potential of the mutant human placental β1,4-galactosyltransferase-1 in the synthesis of multivalent glycomimetics and glycomaterials.

• MeSH
• aktivace lymfocytů účinky léků   imunologie   MeSH
• beta-N-acetylhexosaminidasy metabolismus   MeSH
• biomimetika metody   MeSH
• buňky NK chemie   účinky léků   imunologie   metabolismus   MeSH
• CD antigeny imunologie   metabolismus   MeSH
• diferenciační antigeny T-lymfocytů imunologie   metabolismus   MeSH
• galaktosyltransferasy genetika   metabolismus   MeSH
• imunoprecipitace MeSH
• krysa rodu rattus MeSH
• lektiny typu C agonisté   imunologie   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• molekulární mimikry MeSH
• mutace MeSH
• placenta enzymologie   MeSH
• polysacharidy chemická syntéza   farmakologie   MeSH
• receptory buněk NK agonisté   imunologie   metabolismus   MeSH
• rekombinantní proteiny genetika   metabolismus   MeSH
• těhotenství MeSH
• vazba proteinů účinky léků   imunologie   MeSH
• vazebná místa účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH