Lithocholic Acid Analog-based Sialylation Inhibitor Development at CD BioGlyco

The salivary acid is usually located at the non-reducing end of the oligosaccharide chain. The design and development of sialylation inhibitors have good potential for immunotherapy such as cancer. At CD BioGlyco, we develop sialylation inhibitors based on lithocholic acid analogs.

• Screening of inhibitors
  The lithocholic acid analogs are effective in interfering with the process of sialylation. Therefore, we collect lithocholic acid analogs using high-throughput screening to precipitate potential inhibitors of sialylation. Next, we add the inhibitors to cells or organisms, measure the effects of the inhibitors on sialylation, and screen for lithocholic acid analogs with good inhibitory ability. In this process, we offer methods such as luciferase assay, fluorescent probes, and so on.
• Design and optimization of inhibitors
  We synthesize and optimize the lithocholic acid analogues with good inhibitory ability based on the sieve sequence as a template. Firstly, we design and synthesize the lithocholic acid analogs through a series of processes including esterification, coupling, hydrolysis, reduction, phosphorylation, and peptide side-chain modification of lithocholic acid, using carboxylic acids containing four rings as substrates. Next, we analyze the structure and purify lithocholic acid analogs using various spectroscopic and chromatographic techniques.
• Assessment of biological effects of inhibitors
  • Cell permeability and cytotoxicity
    We test the fluorescence intensity of normal cells and lithocholic acid analog-treated cells and compare the luminescence effect of the two types of cells to obtain the uptake of lithocholic acid analog by cells. Cytotoxicity is analyzed using flow cytometry to test the survival of the cells.
  • Semi-inhibitory concentration
    We diffuse the lithocholic acid analog in DMSO and dilute it in the culture medium to treat the cells. The semi-inhibitory concentration is analyzed using reverse transcription-polymerase chain reaction (RT-PCR).

Fig.1 Lithocholic acid analog-based sialylation inhibitor development. (CD BioGlyco)

Publication

Technology: Novel sialic acid transferase inhibitors derived from lithocholic acid are synthesized and tested for biological activity.

Journal: Journal of Cellular Physiology

IF: 5.6

Published: 2010

Results: Aberrant sialylation catalyzed by sialic acid transferase enzymes (ST) is often found in cancer cells and is associated with increased cancer metastasis. This study synthesized AL10, a novel ST inhibitor derived from lithocholic acid, and investigated the anticancer effects of this compound. AL10 is found to be cell-permeable and effective in attenuating total salivation at the cell surface. The inhibitor is not cytotoxic but inhibits adhesion, migration, actin polymerization, and invasion of A549 and CL1.5 human lung cells overexpressing α-2,3-ST. The inhibition of adhesion and migration by AL10 is associated with a reduction in the sialylation of various integrin molecules and an attenuation of activation of integrin downstream signaling mediators, and adhesion kinases. More importantly, AL10 significantly inhibited experimental lung metastasis in vivo without affecting the liver and kidney functions of experimental animals, as determined by serum biochemical assays.

Fig.2 Effect of AL10 on cell sialylation and α-2,3-ST expression. (Chiang, et al., 2010)

Applications

• Lithocholic acid analog-based sialylation inhibitors can be used in studies to inhibit tumor metastasis in mammals.
• Lithocholic acid analog-based sialylation inhibitors can be used as essential targets for immunotherapeutic drug development research.
• Lithocholic acid analog-based sialylation inhibitors can be used to explore the physiological functions of lithocholic acid analogs.

Advantages

• Our glycosylation inhibitor R&D technology is mature and our R&D solutions are quality tested to provide high-quality glycosylation inhibitor R&D services to our clients.
• Our service team is highly responsive, anticipating client needs and exceeding client expectations to ensure a favorable experience and satisfaction.
• We provide a range of services from synthesis of core compounds to testing of inhibitory effects, saving clients time and effort.

CD BioGlyco is at the forefront of glycosylation inhibitor research and development, offering a wide range of Glycosylation Inhibitor Development Services. We have specialized researchers to create a custom development program for each client. If you are interested in our services, please contact us for more details without any hesitation.