Cytidine Analog-based Sialylation Inhibitor Development at CD BioGlyco

Elevated sialyltransferase activity leads to overexpression of sialic acid on the cell surface and contributes to the development of many diseases such as cancer and inflammation. Cytosine analogs have a favorable inhibitory effect on sialyltransferases. At CD BioGlyco, we provide comprehensive sialylation inhibitor development services to our clients.

• Screening of sialylation inhibitors
  Sialylation is the process of covalent addition of salivary acid to the ends of glycoproteins and participation in the immune response. The process is mediated by sialyltransferases (ST). Whereas, cytosine analogs effectively bind to sialyltransferases, thereby interfering with sialylation. Therefore, we utilize high-throughput screening for cytidine analogs that interfere with sialylation and construct a cytidine analog library. The inhibitory activity of each cytidine analog in the library is evaluated.
• Synthesis of sialylation inhibitors
  We also offer the design and expansion of inhibitors of sialylation. We use compound molecules from cytidine analog libraries as templates for synthesis and modification using chemical and biological means. Similarly, we evaluate the inhibitory effects of the synthesized cytidine analog molecules.
• Evaluation of the effects of sialylation inhibitors
  We provide inhibitor activity assessment services utilizing cellular models or in vitro experimental systems, including experiments to determine inhibitor activity and effects on cytidine analog modification.

Fig.1 Cytidine analog-based sialylation inhibitor development service. (CD BioGlyco)

Publication

Technology: Chemical synthesis, Asymmetric synthesis methods

Journal: Glycoconjugate Journal

IF: 3

Published: 2004

Results: The paper reports the synthesis and inhibition of cytidine analog-based inhibitors of α-2,6-sialyl glycosyltransferase that contain planar isomerized carbons with increased distances between the isomerized carbons and the CMP leaving group and contain at least two negative charges. At the same time, these inhibitors bear single or multiple carboxylate or phosphonate substituents, to evaluate the effect of (i) increasing the relationship between the isomeric carbon of the plane and the CMP leaving group, and (ii) the number of negative charges in the vicinity of the glycosylation cleavage site. In addition, a simple and efficient way of asymmetric synthesis of one of the most promising inhibitors is presented, providing rapid access to a huge number of highly potent, stereochemically pure inhibitors for further biological studies.

Fig.2 Mechanism of sialyl transfer. (Skropeta, et al., 2004)

Applications

• Cytidine analog-based sialylation inhibitors are developed for many physiological activities. Examples include regulation of cell-ligand, microbe-cell interactions, immune modulation, and control of cell activation.
• In medicine, cytidine analog-based sialylation inhibitors can be used in studies against tumors and viral infections.
• Cytidine analog-based sialylation inhibitors can be used in the development of small-molecule drugs.

Advantages

• We have a proven system of inhibitor development services to create the right development program for our clients and ensure their satisfaction.
• Each of our R&D solutions is quality tested and our goal is to meet the needs of our clients beyond their expectations.
• We have the inhibitor development technology that is efficient, easy to operate, and safe.

CD BioGlyco offers our clients a diverse and comprehensive range of services in the field of Glycosylation Inhibitor Development. At the same time, we provide custom glycosylation inhibitor development solutions for each client. Please feel free to contact us if you are interested in our services and have any questions.