The NMR studies of CMP inhibition of polysialylation

Abstract

The overexpression of polysialic acid (polySia) on neural cell adhesion molecules (NCAM) promotes hypersialylation, and thus benefits cancer cell migration and invasion. It has been proposed that the binding between the polysialyltransferase domain (PSTD) and CMP-Sia needs to be inhibited in order to block the effects of hypersialylation. In this study, CMP was confirmed to be a competitive inhibitor of polysialyltransferases (polySTs) in the presence of CMP-Sia and triSia (oligosialic acid trimer) based on the interactional features between molecules. The further NMR analysis suggested that polysialylation could be partially inhibited when CMP-Sia and polySia co-exist in solution. In addition, an unexpecting finding is that CMP-Sia plays a role in reducing the gathering extent of polySia chains on the PSTD, and may benefit for the inhibition of polysialylation. The findings in this study may provide new insight into the optimal design of the drug and inhibitor for cancer treatment.

Keywords:

• Metastatic spread
• polysialic acid
• polysialyltransferase
• polysialyltransferase domain
• chemical shift perturbation

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

We are thankful for the financial support of the financial supports from Guangxi Science and Technology Base and Talents Project (Guike-AA20297007), the National Natural Science Foundation of China (32060216), Guangxi Natural Science Foundation, China (2017GXNSFAA198167), Guangxi Major Science and Technology Innovation Base Construction Project (2018–15-Z03-1203).