Strategies for Sialic Acid Analog-based Sialylation Inhibitor Development

CD BioGlyco is a company specializing in providing Glycosylation Inhibitor Development. We have a professional inhibitor development team to serve you and listen to your every need. Overexpression of sialyltransferases and other glucogenes abnormally sialylate the surface of cancer cells, affecting their apoptosis and metastasis. Our company offers strategies for designing sialic acid analogs that interfere with the cellular sialic acid synthesis machinery to reduce abnormal sialic acids.

• We regulate the expression of sialic acid by inhibiting GNE/MNK activity.
• Meanwhile, the direct blockade of sialyltransferase and blocking of the synthesis of sialic acid indirectly make sialic acid analog global inhibitors of sialylation.

Sialic Acid Analog-based Sialylation Inhibitor Development Service at CD BioGlyco

Since the biological pathway for synthetic donors accepts artificially substituted monosaccharides, therefore, we spread sialyltransferase into the cell by passive synthesis. Intracellular inhibitors can be formed by deacetylating the corresponding donor analog. Furthermore, due to the structural similarity of sialic acid analog to the natural substrate, we regulate de novo synthesis through a feedback loop. This step promotes the reconstitution of cell surface carbohydrates. Our dual mechanistic service enhances the generalizability and specificity of inhibitors with greater effects than simple inhibitors.

• Inhibitor titrations service: For treated cells, flow cytometry analysis is performed with various lectins or antibodies against glycans (anti-glycans).
• Recovery of sialylation and a sialyltransferase substrate competition assay: Cell surface sialylation is assessed using a conjugated lectin.
• Analysis of inhibitor-treated cells: We provide precise mass spectrometry (MS) and nucleotide sugar analysis services for inhibitor-treated cells.
• Tumor mouse model: In addition, we provide tumor mouse models for inhibitor activity assessment. The pooled buffer is treated with sialylated analogs and injected into the mice. The tumor condition is observed at all times. After the tumor volume reaches the standard, kill the mice.

Fig.1 Schematic diagram of the analysis of inhibitor-treated cells. (CD BioGlyco)

Publication

Technology: Flow cytometry

Journal: Nature Chemical Biology

IF: 14.8

Published: 2012

Results: Specifically focused epitopes by using antibodies and lectin detection. Treatment of the cells by flow cytometry revealed that Lewis X and SLeX were almost completely unobserved and showed a significant reduction in sialyl T antigen. Furthermore, the inhibitor also completely abolished SLeX staining, reflecting the inhibition of ST3Gal IV, ST3Gal VI, or both. Finally, the effect of the inhibitor on ST6Gal I was tested by generating large amounts of Neu5Acα2-6 Gal from the plant lectin, and the inhibition of this epitope was found to be stable at the 30% control. In summary, metabolic sialyltransferase and FUT inhibitors largely affect the characteristics of leukocytes.

Fig.2 Fluorinated fucose and sialic acid analogs act as fucosyl- and sialyltransferase inhibitors in cells. (Rillahan, et al., 2012)

Applications of Sialic Acid Analog-based Sialylation Inhibitor

• Sialic acid analog-based sialylation inhibitor effectively inhibits sialylation after uptake in human leukemia cells.
• Sialic acid analog-based sialylation inhibitor significantly reduces the expression of the sialylated and focused ligand sialyl Lewis X on myeloid cells, resulting in a loss of selectin binding and impaired leukocyte rolling.
• Sialic acid analog-based sialylation inhibitor modulates sialidin expression in vivo and is an important tool for exploring sialic acid in health and disease.
• Sialic acid analog-based sialylation inhibitor plays a key role in liver and kidney function and can be used as a mediator for the growth and development of cells in the liver and kidney.

CD BioGlyco has been serving in the field of inhibitor development for many years. We have comprehensive inhibitor development solutions and a team of professionals to help our clients complete their projects. Moreover, we provide high-quality Capping Modification Inhibitor Development services including Fucosylation Inhibitors and Sialylation Inhibitors. If you need anything, please feel free to contact us.