The selectins are a small family of transmembrane Glycoproteins. By combining with the carbohydrate ligands on the cell surface, they mediate cell-cell adhesion. At present, there are three species have been identified. They are each expressed in a different subset of cells: P-selectin (platelets and endothelial cells), L-selectin (leukocytes), and E- selectin (endothelial cells). They are also known by their cluster of differentiation (CD) antigen designations CD62P, CD62E, and CD62L. There are several similar structural features of three selectin proteins, such as a calcium-dependent (C-type) lectin binding domain, an epidermal growth factor (EGF)-like domain, a series of short consensus complement regulatory (CR) protein repeat sequences, and a transmembrane anchor segment. The number of CR repeats and the size of their cytoplasmic domains vary. The ligands for the selectins are cell surface Glycoproteins that present clusters of specialized Oligosaccharides. L-selectin is known to bind GlyCAM-1, CD34, and MAdCAM-1; each is expressed on distinct tissues and each presents many L-selectin binding sites distributed over the length of the scaffold. In comparison, TSI, the P-selectin ligand, is a dimer that presents a single binding site at the tip of each subunit. E-selectin ligands have not yet been identified, but candidates include the E-selectin-specific ESL-1 and the shared ligand, TSI.
The first procedure is launching the inflammation selectin-mediated leukocyte adhesion to endothelial. That is a potential target for specific therapies. The development of several selectin inhibitors has facilitated the research of selectin involvement in inflammation, including monoclonal antibodies, Carbohydrates, small molecule inhibitors, and soluble forms of P-selectin glycoprotein ligand 1.
Small molecule selectin inhibitors are molecules with a molecular weight of < 900 Da. Efomycine M is a kind of small-molecule inhibitor. It can inhibit leukocyte adhesion mediated by selectin in vitro and in vivo. And inflammatory disorders are alleviated vastly in vivo. Efomycine M is the lead compound of a new family of agents. It interferer leukocyte-endothelial cell adhesive interactions which are mediated by selectins. Consequently, efomycine M has demonstrated profound interference with selectin-mediated leukocyte adhesion that resulted in diminished leukocyte rolling in blood vessels in vivo as well as in alleviation of inflammation in two complementary mouse models of psoriasis. To assess other small-molecule selectin inhibitors which are the family of efomycine, several new species of this family were purified. The naturally occurring components of the Streptomyces BS1261 fermentation material were purified by HPLC and analyzed by thin-layer chromatography, reversed-phase HPLC, proton nuclear magnetic resonance (1H-NMR) spectroscopy, and fast atom bombardment (FAB)-mass spectrometry (MS). Two naturally occurring compounds could be isolated: efomycine E and efomycine G. The two species could be purified in quantities sufficient for cell adhesion experiments. When the functional activity of efomycines on the adhesion of leukocytes to vascular endothelium was studied, efomycines E, and G, significantly inhibited the adhesion of both human and porcine leukocytes to the vascular endothelium. Thus, it proves the utility of these small-molecule selectin inhibitors for inflammation.
Fig.1 Structures of efomycine species. (Wienrich, et al., 2006)
Small molecule selectin inhibitors include but are not limited to Pan-selectin antagonists, PSGL1 mimetic inhibitor, and E-selectin-specific inhibitor.
Small molecule selectin inhibitors have great potential for treating human diseases. CD BioGlyco's ascensive glycosylation inhibitor development platforms provide custom services to customers all over the world. We have many outstanding researchers to make plans according to customer requirements. If you are interested in our services, please feel free to contact us for more detailed information.
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