Design, synthesis and neurite outgrowth activity of novel ganglioside GM1 derivatives by remodeling of the fatty acid moiety

Chen, Xiaohui; Jin, Xuefeng; Huang, Feng-Tao; Wang, Juntao; Cao, Xuefeng; Wang, Peng George; Feng, Yue; Jiang, Faqin; Yang, Guangyu

doi:10.1016/j.ejmech.2022.114636

Cited by 3 publications

(1 citation statement)

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“…This finding will facilitate further biological investigations of this analogue in the future due to its synthetic efficiency, achieved through three-step enzymatic glycosylations from lactoside, resulting in a high overall yield. While the previous investigation proposed that the ceramide moiety of GAA-7 lacks significance in neuritogenic activity, some reports highlight concerns about the impact of the ceramide moiety on GM1a ganglioside activity. , Nonetheless, this modular enzymatic synthesis offers an easily accessible method for assembling sugars to generate GAA-7 glycan derivatives with diverse aglycone ceramides, paving the way for future neurobiological studies.…”

Section: Discussionmentioning

confidence: 99%

Chemoenzymatic Synthesis of GAA-7 Glycan Analogues and Evaluation of Their Neuritogenic Activities

Tseng,

Su,

Lai

et al. 2024

ACS Chem. Neurosci.

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Ganglioside GAA-7 exhibits higher neurite outgrowth than ganglioside GM1a and most echinodermatous gangliosides (EGs) when tested on neuron-like rat adrenal pheochromocytoma (PC12) cells in the presence of nerve growth factor (NGF). The unique structure of GAA-7 glycan, containing an uncommon sialic acid (8-O-methyl-N-glycolylneuraminic acid) and sialic acid-α-2,3-GalNAc linkage, makes it challenging to synthesize. We recently developed a streamlined method to chemoenzymatically synthesize GAA-7 glycan and employed this modular strategy to efficiently prepare a library of GAA-7 glycan analogues incorporating N-modified or 8-methoxyl sialic acids. Most of these synthetic glycans exhibited moderate efficacy in promoting neuronal differentiation of PC12 cells. Among them, the analogue containing common sialic acid shows greater potential than the GAA-7 glycan itself. This result reveals that methoxy modification is not essential for neurite outgrowth. Consequently, the readily available analogue presents a promising model for further biological investigations.

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Section: Discussionmentioning

confidence: 99%