Chemoenzymatic synthesis and biological evaluation of ganglioside GM3 and lyso-GM3 as potential agents for cancer therapy

ST3GAL5‐catalyzed gangliosides inhibit TGF‐β‐induced epithelial‐mesenchymal transition via TβRI degradation

“…In addition, these findings, taken together with the TGF-b-induced decrease in a-series gangliosides, indicate that these gangliosides participate in a self-enabling response of EMT promoted by TGF-b. Consistent with our results, chemoenzymatically synthesized GM3 effectively inhibited the migration of melanoma B16-F10 cells (Li et al, 2021). In addition, GM3 synthase overexpressing A2780 ovarian carcinoma cells were characterized by increased levels of caveolin-1 and reduced motility in vitro (Prinetti et al, 2011).…”

One-Pot Enzymatic Synthesis and Biological Evaluation of Ganglioside GM3 Derivatives as Potential Cancer Immunotherapeutics

“…Gangliosides are closely related to the proliferation, movement, migration, adhesion, apoptosis, and immune escape of cancer cells. , Various types of gangliosides are typically expressed on the surface of cancer cells, called tumor-associated carbohydrate antigens. − Among these, the simplest ganglioside GM3 (NeuAca3Galb4Glcb1Cer) is closely associated with human tumors, especially malignant tumors. ,− The expression of GM3, which is not detected in normal melanocytes, is increased in primary and metastatic melanoma . Saha et al demonstrated that the ability of B16 mouse melanoma cells to metastasize and invade has increased, as the cell surface exhibits a high level of GM3 expression. , Some GM3 derivatives have already been found having inhibitory effects on tumor cell growth and migration in vitro . , Because of its important roles in the process of tumor development, GM3 has been validated as a promising target for cancer immunotherapy …”

“…Compared to laborious chemical methods, highly selective and specific enzymatic synthesis has proven to be a promising method by avoiding the necessity of numerous protecting group strategies . In this regard, enzymatic synthesis is much more favored. , However, methods reported by Chen’s , and Meng’s groups involved the synthesis of lactose-sphingosine with 11 and 10 chemical steps, respectively. The acylation of lyso-GM3 and derivatives with a fatty acid was also performed by chemical synthesis.…”

“…22,23 Some GM3 derivatives have already been found having inhibitory effects on tumor cell growth and migration in vitro. 24,25 Because of its important roles in the process of tumor development, GM3 has been validated as a promising target for cancer immunotherapy. 26 Effective immunotherapy relies on the choice of the antigen, and gangliosides, especially GM3, play an important role in it.…”

“…41 In this regard, enzymatic synthesis is much more favored. 42,43 However, methods reported by Chen's 39,40 and Meng's 25 groups involved the synthesis of lactose-sphingosine with 11 and 10 chemical steps, respectively. The acylation of lyso-GM3 and derivatives with a fatty acid was also performed by chemical synthesis.…”