The polysialic acid (polySia) is a unique carbohydrate polymer produced on the surface
of Neuronal Cell Adhesion Molecule (NCAM) in a number of cancer cells, and strongly correlates
with the migration and invasion of tumor cells and with aggressive, metastatic disease and poor
clinical prognosis in the clinic. Its synthesis is catalyzed by two polysialyltransferases (polySTs),
ST8SiaIV (PST) and ST8SiaII (STX). Selective inhibition of polySTs, therefore, presents a therapeutic
opportunity to inhibit tumor invasion and metastasis due to NCAM polysialylation. It has
been proposed that NCAM polysialylation could be inhibited by two types of heparin inhibitors,
low molecular heparin (LMWH) and heparin tetrasaccharide (DP4). This review summarizes how
the interactions between Polysialyltransferase Domain (PSTD) in ST8SiaIV and CMP-Sia, and between
the PSTD and polySia take place, and how these interactions are inhibited by LMWH and
DP4. Our NMR studies indicate that LMWH is a more effective inhibitor than DP4 for inhibition
of NCAM polysialylation. The NMR identification of heparin-binding sites in the PSTD may provide
insight into the design of specific inhibitors of polysialylation.
Keywords: Cancer, NCAM polysialylation, Polysialyltransferase (polyST), ST8SiaIV, Heparin, Inhibitor, Polysialyltransferase
Domain (PSTD), NMR, Chemical Shift Perturbation.
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