关键词: NMR spectroscopy cancer cell migration chemical shift perturbation (CSP) neuronal cell adhesion molecule (NCAM) polysialic acid (polySia) polysialyltransferase (polyST) polysialyltransferase domain (PSTD) sialylactose (SL)

来  源:   DOI:10.3390/cimb46060340   PDF(Pubmed)

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.
摘要:
众所周知,哺乳动物中的唾液酸乳糖(SL)是唾液酸(Sia)的主要来源,它可以进一步形成胞苷一磷酸唾液酸(CMP-Sia),并且最终产物是在神经细胞粘附分子(NCAM)上使用聚唾液酸转移酶(polySTs)的聚唾液酸(polySia)。该过程称为NCAM聚唾液酸化。多唾液酸化的过度表达与癌细胞迁移密切相关。入侵,和转移。为了抑制聚唾液酸化的过度表达,在这项研究中,选择SL作为抑制剂以测试聚唾液酸化是否可以被抑制。我们的结果表明,当3'-唾液酸乳糖(3'-SL)或6'-唾液酸乳糖(6'-SL)浓度约为0.5mM或6'-SL和3mM时,可以抑制polyST和CMP-Sia中的聚唾液酸转移酶结构域(PSTD)与PSTD和polySiia之间的相互作用。分别。结果还表明,与另外两种抑制剂相比,SL(特别是3'-SL)是理想的抑制剂。低分子量肝素(LMWH)和胞苷一磷酸(CMP),因为3'-SL不仅可以用于抑制NCAM多聚唾液酸化,但也是婴儿配方奶粉和肠道健康系统的最佳补充剂之一。
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