Selectins are differentially expressed carbohydrate-binding Proteins. They are a family of three molecules, that are E-selectin, P-selectin, and L-selectin. Three known selectins are presented in different subsets of cells: P-selectin is expressed on the surface of activated platelets and endothelial cells, L-selectin constitutively emerges on leukocytes, and E-selectin synthesis is come out in activated endothelial cells. Cells within blood vessels can be regulated interactions by with selectins. Thus, they can accelerate the adhesion of blood cells (white blood cells, platelets, and red blood cells) to the walls of blood vessels and each other. For this reason, they are known as adhesion molecules. By interacting specifically with clusters of Oligosaccharides presented on cell surface Glycopeptide ligands, they mediate cell-cell adhesion in the shear flow of the bloodstream. Therefore, selectin can mediate the adhesion of hemocytes to the vascular endothelium.
The leukocytes on the vascular endothelium are mediated to tether and roll because of selectins. This process is one of the key factors causing the inflammatory response. Hence, they constitute a promising target for the therapeutic modulation of inflammation. At the same time, selectins play a pivotal role in curing vaso-occlusion. Consequently, selectin inhibition is to be an excellent target of drug discovery programs at many pharmaceutical and biotechnology companies. The involvement of the selectins in various disease states has promoted the advancement and rational design of drugs. The role of selectin-ligand interactions in the inflammatory response has been demonstrated in various animal models, prompting considerable attention from the pharmaceutical industry. Nowadays a lot of classes of selectin inhibitors have been yielded, such as soluble protein ligands, Antibodies, oligosaccharides, and small molecules.
A new pan-selectin antagonist with better pharmacological properties was synthesized, based on recent progress in the understanding of molecular interaction between selectins and their natural ligands as well as progress in the development of synthetic antagonists. Based on the existing pan-selectin antagonist template structure, a ligand-based method followed by focused chemical synthesis has been applied to synthesize novel pan-selectin antagonists which bear a trihydroxy benzene motif and do not bear peptidic nor Glycosidic components, with nanomolar in vitro activity.
Fig.1 New pan-selectin antagonist (Kranich, et al., 2007)
Two kinds of in vitro assays were used to biologically evaluate the compounds presented here. Biological evaluation involves two in vitro assays, a static molecular binding assay, and a dynamic HL-60 cell attachment assay. the new pan-selectin antagonist showed better biological in vitro activity both under static and dynamic conditions, compared to controls.
In conclusion, pan-selectin antagonists have great potential to treat diseases. As a provider for molecule synthesis, CD BioGlyco concentrates on the development of methodologies according to customer requirements to help them press forward on deeper research. If you need scientific help, please feel free to contact us.
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