Carbohydrate Click-based Selectin Antagonist Development Service
Unlocking Selectin Inhibition with Carbohydrate Click Chemistry
CD BioGlyco is well established in the field of click chemistry, which we also effectively combine with Drug Development, such as Enzyme Inhibitor Development and Lectin Ligand Development. Here, we provide high-quality carbohydrate click-based selectin antagonist development services to our clients.
- Various heterocyclic analogs have been identified as potential precursors of selectin antagonists. We utilize click chemistry, i.e., copper(I)-catalyzed cycloaddition reactions of azides with appropriate alkynes, to prepare triazolyl analogs and further develop them as selectin antagonists. Generally, we use water/butanol mixtures as solvents for this reaction, which allows simple separation of the desired compounds precipitated from the reaction medium.
Most antagonists have some structural features in common. In most cases, they are planar, aromatic, or π-electron rich and nitrogen-containing heterocycles. In this procedure, we provide multidimensional nuclear magnetic resonance, infrared spectroscopy, and quadrupole/orthogonal acceleration time-of-flight tandem mass spectrometer to accurately measure the structure and molecular weight of the prepared compounds.
- Next, we provide an evaluation of their biological activity. Examples include affinity, selectivity, and potency.
We use trypsinization to obtain Chinese hamster ovary (CHO) cells expressing recombinant glycoproteins and co-cultivate the synthesized triazolyl analogs, selectins, and CHO cells. Next, they are tested for their binding affinity to ligands on the surface of selectin to determine their relative effectiveness in activating the ligands. We provide full competition curves to evaluate the binding affinity of the compounds on the ligands.
To explore the structural basis of the binding affinity of these compounds used as selectin antagonists, we provide selectin ligand cell models for computational research on ligand docking. In the process, we also provide binding conformations of the compounds, as well as binding site analysis.
In addition, we provide scintillation spectroscopy to determine the radioactivity of antagonists bound to selectin ligands.
- Furthermore, we also provide chemical modifications to broaden the composition of antagonists. For example, different substituents are introduced to the compounds. Similarly, we evaluate the biological activity of these modified compounds.
Fig.1 Development of selectin antagonists by carbohydrate clicking method. (CD BioGlyco)
Publication Data
Technology: Click chemistry
Journal: Journal of Medicinal Chemistry
IF: 7.3
Published: 2006
Results: The authors have synthesized two series of 2-(1,2,3-triazolyl)adenosine derivatives using click chemistry. Binding affinities as well as relative efficacies of these compounds were then determined at different human adenosine receptors. It was shown that some of the triazole-1-yl analogs exhibited high affinity, and selectivity in the low nanomolar range. In addition, the 5'-OH ethyluronamide analogs (Fig. 2) exhibited increased receptor affinity and behaved as full antagonists.
Fig.2 Structure of 5'-OH ethyluronamide analogs. (Cosyn, et al., 2006)
Applications
- Carbohydrate click-based selectin antagonist development can be used to develop drugs, such as those for allergic inflammation or asthma.
- Carbohydrate click-based selectin antagonist development can be used to probe deeply into the process of inflammatory diseases, and immune disorders.
- Selectin antagonists recognize cell surface glycans, therefore, carbohydrate click-based selectin antagonist development can be used to probe cell surface signaling.
Advantages
- We have world-leading click chemistry technology to support our clients' research in a wide range of areas.
- Our R&D team consists of experts in chemistry and biology to provide custom selectin antagonist development solutions.
- We produce products with high purity and stability.
CD BioGlyco has state-of-the-art click chemistry technology and provides each client with a high-quality lectin ligand development service. All of our protocols are developed by experienced biologists and chemists, and the protocols have passed rigorous quality testing. Please feel free to contact us if you are interested in more details.
References
- Cosyn, L.; et al. 2-Triazole-substituted adenosines: a new class of selective A3 adenosine receptor agonists, partial agonists, and antagonists. Journal of Medicinal Chemistry. 2006, 49(25): 7373-7383.
- Thirumurugan, P.; et al. Click chemistry for drug development and diverse chemical-biology applications. Chemical Reviews. 2013, 113(7): 4905-4979.
For research use only. Not intended for any clinical use.
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