Enzymatic Synthesis of Carbohydrate Ligands for Natural Killer Cells

The Way from Ligand Optimisation Towards Anticancer Glycodrugs
  • Vladimir Kren
Conference paper
Part of the NATO Science Series book series (NAII, volume 129)


Aminosugars have high affinity for the NKR-P1A protein, the major activating receptor at the surface of rat natural killer (NK) cells. We have systematically investigated the structural requirements of the recombinant soluble dimeric form of the receptor for its optimal carbohydrate ligands. The IC50 value for the GalNAcβl→MManNAc disaccharide was nearly 10−10 M with a further possible increase depending on the type of the glycosidic linkage and the aglycon nature.

To speed up the screening and optimization procedure, a combination of quite simple chemical methods with enzymatic ones was used. Enzymatic methods are more straightforward than chemical ones, avoiding tedious protection/deprotection procedures. Quantities in the range of 10 — 100 mg necessary for characterisation, biological tests, and further modification can be quickly obtained by this approach.

The paper should demonstrate basic strategy of the glyco-drug design using chemical and enzymatic methods, receptor binding studies based on the receptor model, immunological and cytological methodologies and finally transfer of the results from in vitro to in vivo systems and design of the compound useful in human therapy in cancer treatment (colon cancer, melanoma).


Natural Killer Cell Aspergillus Oryzae Free Sugar Human Natural Killer Cell Muramic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Vladimir Kren
    • 1
  1. 1.Institute of Microbiology, Laboratory of BiotransformationAcademy of Sciences of the Czech RepublicPrague 4Czech Republic

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