α-1,2-Fucosyltransferase Inhibitor Development Service at CD BioGlyco

α-1,2-Fucosyltransferase is a rate-limiting enzyme that is associated with cancer and catalyzes the synthesis of cell membrane-associated carbohydrate antigens. Often changes in the expression and activity of α-1,2-fucosyltransferases are linked to the production of certain diseases. At CD BioGlyco, we will investigate fucosylation and develop α-1,2-fucosyltransferase inhibitors.

CD BioGlyco provides a variety of α-1,2-fucosyltransferase inhibitor development services and performs synthesis and structural optimization of screened inhibitors to improve inhibitor selectivity and affinity.

• First, we set up an inhibitor library centered on compounds that specifically bind to and interact with α-1,2-fucosyltransferase.
• Then, the inhibitory effects of the compounds in the library are evaluated by in vivo experiments in animal models and cellular models.

Depending on the form of binding to α-1,2-fucosyltransferase, we provide irreversible inhibitors and reversible inhibitors. The former binds to the enzyme through the form of covalent bonding, and the inhibitory effect of this binding mode on α-1,2-fucosyltransferase activity is irreversible. Reversible inhibitors, on the other hand, bind to α-1,2-fucosyltransferase through non-covalent bonds (e.g., hydrogen bonding, hydrophobic interactions, etc.), a form of binding that is not chemically reactive and can be removed by dilution or dialysis, and the inhibitory effect on enzyme activity is reversible.

Fig.1 Development steps of α-1,2-fucosyltransferase inhibitor. (CD BioGlyco)

Publication

Technology: Protein O-fucosylation

Journal: Current opinion in structural biology

IF: 6.8

Published: 2019

Results: The structures of multiple EGF repeats and TSRs modified with O-focused glycans suggest a potential mechanism by which FUT1- or FUT2-mediated focused glycosylation ensures efficient secretion of target proteins. Unlike many carbohydrate modifications, O-focused glycans are very visible in the crystal structures of EGF repeats and TSR, and to some extent, they have been termed "substituted amino acids" because they show similar thermal mobility to potential amino acids (based on the B factor). Fucoidan residues are located on the surface of the EGF or TSR structural domains and have several contacts with potential amino acids. In the absence of O-fucosylation site addition, the secretion defect is likely due to the structural domains re-entering the "folding cycle", which ultimately slows down the rate of folding. In addition, the disaccharide protects the disulfide bond from the surrounding endoplasmic reticulum folding/unfolding environment. This may explain how the addition of glucose provides additional stabilization of the TSR.

Fig.2 EGF repeats and TSRs are modified by O-fucose glycans. (Holdener & Haltiwanger, 2019)

Applications

• In the field of biomedical research, the study of O-fucosylation can be used to probe the structure of fucose and the interactions between glycans and proteins.
• In the field of medical diagnostics, α-1,2-fucosyltransferase inhibitors may be used in the development of research for certain diseases, such as cancer.

Advantages

• Our research team is experienced and has a more mature system for the development of transferase inhibitors to ensure client satisfaction.
• We have excellent process development, optimization, and scale-up technologies.
• We have the world's leading inhibitor development technology, and our technology is characterized by high efficiency and stability.

CD BioGlyco relies on advanced technology to provide our clients with high-quality and efficient Glycosylation Inhibitor Development services. If you are interested in our services, please feel free to contact us.

Quick Links

Resources