Desialylation Inhibitor Development Service at CD BioGlyco

Desialylation refers to the process by which the enzyme sialidase shears off the sialic acid at the ends of the glycan chains of glycoproteins. This process exposes glycan ligands on the surface of the cell membrane, which are then recognized and removed by the desialylated glycoprotein receptors of other cells. At CD BioGlyco, we provide our clients with desialylation inhibitor development services and explore the mechanisms by which desialylation occurs.

• Screening and characterization of inhibitors
  Sialidase is a key player in the desialylation process. First, we collect compounds that bind to sialidase through existing literature data or high-throughput screening, and screen for compounds with inhibitory potential. Then, we test the inhibitory ability of these compounds using cellular models or animal models to further screen for good inhibitors of desalination.
• Optimization of inhibitors
  Based on the screened inhibitor structures, we use chemical and biological methods to modify and optimize their structures to further expand the range of inhibitors.
• Evaluation of the effects of inhibitors
  We utilize flow cytometry (FCM) to detect the ability of inhibitors for desialylation and to compare the survival status of cells before and after desialylation occurs. We also detect cellular autoantibodies using the monoclonal antibody-specific capture antigen technique, which is used to test the role of desialylation production and its relationship with autoantibodies.

Fig.1 Development contents of the desialylation inhibitors. (CD BioGlyco)

Publication

Technology: Multiple myeloma (MM) cells are treated with salivarylase neuraminidase and tests for changes in cellular toxicity.

Journal: Blood

IF: 20.3

Published: 2019

Results: MM cells are treated with salivarylase neuraminidase before co-culture with primary natural killer (NK) cells. Siglec-7 is knocked down using the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system and pre-designed guide RNAs. MM cells are also treated with daratumumab before co-culture with expanded PNK cells. It is concluded that desialylation with neuraminidase leads to increased degranulation of NK cells compared to sugar buffer control. The high degree of sialylation of MM cells facilitates immune evasion, and targeting the removal of sialic acid strongly enhances the cytotoxicity of NK cells against MM.

Applications

• Desialylation inhibitors can be used in therapeutic studies for clinical syndromes of thrombocytopenia due to abnormal autoimmune function.
• Desialylation inhibitors can be used to affect cell-cell interactions. For example, receptors for glycoproteins on the surface of platelet membranes act in conjunction with macrophages.
• Desialylation inhibitors can be used to explore the physiological activities of salivary acid enzymes.

Advantages

• Our research team has experience in Glycosylation Inhibitor Development and is responsive and proactive in providing custom desialylation inhibitor development solutions.
• We design and synthesize desialylation inhibitors with high specificity, permeability, and stability.
• With our strong data resources, we provide inhibitor development services to ensure client satisfaction.

At CD BioGlyco, our glycosylation inhibitor development service keeps abreast of technological trends and provides solutions to ensure that every client saves time and effort in developing inhibitors. With our professional research team in the field of glycobiology, we are confident to be your right hand in the field of glycobiology. If you are interested in our services, please feel free to contact us.