Certain cancer cells are able to evade immune detection by decorating their cell surface with sialylated glycans . The disialylated ganglioside disialosyl globopentaosylceramide (DSGb5, Fig 1) has been found on renal cancer cells and is correlated with a higher migration potential. A proposed mechanism of the immune evasion of DSGb5 is by binding sialic acid-binding immunoglobulin-type lectin (Siglec)-7 on NK-cells. Siglec-7 is a surface receptor which, upon ligand binding, inhibits an immune response through its intracellular tyrosine-based inhibition motif (ITIM) domain. So far, DSGb5 binding to Siglec-7 has only been studied in cell systems [2,3]. Knowing how pure DSGb5 binds Siglec-7 will give us insight on important structural features and can help us to design an possible inhibitor.
To obtain enough pure of the ganglioside an chemical synthetic approach is proposed for the core pentasaccharide Gb5. Neuraminic acids, however, are known to be difficult to handle in chemical synthesis due to the deactivating C-1 carboxylic acid on the anomeric position and absence of participating groups at C-3. Therefore an enzymatic approach will be used to install these monosaccharides in a site- and stereoselective way. A linker was installed at the reducing end to immobilize the glycan on a NHS-activated microarray slides and binding with Siglec-7 will be studied.
- Büll, C.; Stoel, M. A.; den Brok, M. H.; Adema, G.J. Cancer Res. 2014, 15, 3199-3204
- Ito, A.; Handa, K.; Withers, D. A.; Satoh, M.; Hakomori, S. FEBS Letters. 2001, 498, 116-120
- Kawasaki, Y.; Ito, A.; Withers, D. A.; Taima, T.; Kakoi, N.; Saito, S.; Arai, Y. Glycobiology. 2010, 20, 1373-1379