Professional GlycoCLICK™-based Neuraminidase Inhibitor Development Rely on Reliable Principles

CD BioGlyco has a professional development team and advanced instruments to provide GlycoCLICK™-based Drug Development services such as Enzyme Inhibitor Development and Carbohydrate Click-based Lectin Ligand Development. Neuraminidase is an important functional glycoprotein embedded in the surface of the envelope of influenza viruses. The neuraminidase active site directly interacts with the substrate neuraminic acid and participates in the glycosidic bond-catalyzed hydrolysis process, so it is an ideal target for inhibitor development. Based on click chemistry, CD BioGlyco utilizes the location of the drug target on the viral surface and the conserved structure of the active site to design and develop neuraminidase inhibitors.

• Inhibitor Design and Synthesis
  Our professional synthesis team provides design and synthesis services for many types of neuraminidase inhibitors. We synthesize triazolyl derivatives using cu-catalyzed azide-alkyne cycloaddition (CuAAC) starting from C9-azido-2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) methyl ester.
  Our lab prepares 1,2,3-triazole-bis-sialic acid derivatives using copper-catalyzed azide-alkyne cycloaddition reactions with α-sialic acid azides as substrates. This key intermediate is attached to various alkyne-based scaffolds via "click chemistry" to obtain multivalent sugar clusters.
• Inhibition Assay
  We evaluate the potential of the synthesized compounds as neuraminidase inhibitors using 96-well plate fluorescence analysis for micromolar half-inhibitory concentration values.
  We determine the inhibitory activity of the target compounds by 2'-(4-Methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) as a substrate to determine the inhibitory activity of the target compound using chemiluminescence.

Publication

Applications

• Isozyme-selective inhibitors of human neuraminidases are potential tools to study the biological functions of these enzymes.
• The development of new neuraminidase inhibitors becomes a very important target for increasing the control of known serotypes and for preventing the spread of a new pandemic.
• GlycoCLICK™-based neuraminidase inhibitor promotes neurotransmitter transmission and improves the functioning of the nervous system. It plays a very important physiological role in the brain.
• GlycoCLICK™-based neuraminidase inhibitor selectively inhibits respiratory virus surface neuraminidase activity and prevents replication and release of progeny virus particles in human cells.

Frequently Asked Questions

• How the neuraminidase inhibitors interfere with the viral infection?

Neuraminidase inhibitors selectively inhibit neuraminidase activity on the viral envelope by competing with sialic acid, the natural substrate of neuraminidase. In doing so, it blocks the enzyme's active site and inhibits neuraminidase cleavage. Ultimately, it prevents the shedding of viral particles from infected host cells, thereby reducing viral replication and transmission in the body.

• What are the active sites of neuraminidase?

Neuraminidase is a tetramer of identical subunits, structurally divided into four parts: the tail, the transmembrane domain, the stem, and the bulbous head. The active site of neuraminidase is the polar active site consisting of an arginine residue, an aspartate residue, and a glutamate residue, as well as four hydrophobic residues. The active site of all influenza neuraminidases contains three key arginine residues (Arg118, Arg292, and Arg371) that bind to the carboxylic acid of the substrate, salivary acid. These residues provide positive electricity and a hydrogen bond formation environment, facilitating the binding to the anionic substituent in the inhibitor.

CD BioGlyco has a professional development team and advanced instruments to help our clients develop a variety of enzyme inhibitor. Our highly synthetic experience staff completes the project with high-efficiency and high-quality. Please feel free to contact us.

• GlycoCLICK™-based Protein Tyrosine Phosphatase (PTP) Inhibitor Development Service
• GlycoCLICK™-based Protein Kinase Inhibitor Development Service
• GlycoCLICK™-based Fucosyltransferase Inhibitor Development Service
• GlycoCLICK™-based Mannosyltransferase Inhibitor Development Service
• GlycoCLICK™-based Nicotinamide Phosphoribosyltransferase Inhibitor Development Service
• GlycoCLICK™-based O-GlcNAcase Inhibitor Development Service
• GlycoCLICK™-based Glycogen Phosphorylase Inhibitor Development Service
• GlycoCLICK™-based Glycosidase Inhibitor Development Service