NMR Studies of the Interactions between Sialyllactoses and the Polysialytransferase Domain for Polysialylation Inhibition

TL;DR

This study explores how sialyllactoses can inhibit polysialylation, a process linked to cancer cell spread, and finds that 3′-sialyllactose is a promising inhibitor and supplement.

Contribution

The study identifies 3′-sialyllactose as a novel and effective inhibitor of polysialyltransferase activity compared to existing inhibitors.

Findings

3′-SL and 6′-SL inhibit interactions between polysialyltransferase domain and CMP-Sia or polySia at specific concentrations.

3′-SL is more effective than LMWH and CMP in inhibiting NCAM polysialylation.

3′-SL has dual benefits as an inhibitor and a supplement for gut health.

Abstract

It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3′-sialyllactose (3′-SL) or 6′-sialyllactose (6′-SL) concentration is about 0.5 mM or 6′-SL and 3 mM, respectively. The results also show that SLs (particularly for 3′-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3’-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.

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