Abstract
Selectins are type-I transmembrane glycoproteins that are ubiquitously expressed on activated platelets, endothelial cells, and leukocytes. They bind to cell surface glycoproteins and extracellular matrix ligands, regulate the rolling of leukocytes in the blood capillaries, and recruit them to inflammatory sites. Hence, they are potential markers for the early detection and inhibition of inflammatory diseases, thrombosis, cardiovascular disorders, and tumor metastasis. Fucosylated and sialylated glycans, such as sialyl Lewisx, its isoform sialyl Lewisa, and heparan sulfate, are primary selectin ligands. Functionalization of these selectin-binding ligands on multivalent probes, such as nanoparticles, liposomes, and polymers, not only inhibits selectin-mediated biological activity but is also involved in direct imaging of the inflammation site. This review briefly summarizes the selectin-mediated various diseases such as thrombosis, cancer and recent progress in the different types of multivalent probes used to target selectins.
Highlights
The first report of blood cells rolling, adhesion and migration on activated endothelial cell surfaces under shear flow conditions came over a decade ago (Chiara et al, 1999)
P-Selectin glycoprotein ligand-1 (PSGL-1) is a homodimer protein expressed on cell surfaces that undergoes posttranslational modification with sialyl Lewisx (SLex) glycan at N-terminals and binds to the selectin carbohydrate-recognition domain (CRD) to regulate the tethering, rolling, and adhesion of leukocytes at the inflammatory site (McEver and Zhu, 2010)
Several biomimetic analogs of SLex and HS, such as quinic acid and fucoidan (Amoozgar et al, 2013), have been reported as potential ligands that target selectins. Polypeptide sequences such as IELLQAR showed strong inhibition of sialyl LewisX binding to E-selectin, as endothelial cell-leukocyte interaction and platelet-leukocyte interaction are involved in coagulation, inflammation, and metastasis (Chapon et al, 2009)
Summary
Selectins are type-I transmembrane glycoproteins that are ubiquitously expressed on activated platelets, endothelial cells, and leukocytes They bind to cell surface glycoproteins and extracellular matrix ligands, regulate the rolling of leukocytes in the blood capillaries, and recruit them to inflammatory sites. They are potential markers for the early detection and inhibition of inflammatory diseases, thrombosis, cardiovascular disorders, and tumor metastasis. Fucosylated and sialylated glycans, such as sialyl Lewisx, its isoform sialyl Lewisa, and heparan sulfate, are primary selectin ligands Functionalization of these selectin-binding ligands on multivalent probes, such as nanoparticles, liposomes, and polymers, inhibits selectin-mediated biological activity but is involved in direct imaging of the inflammation site. This review briefly summarizes the selectin-mediated various diseases such as thrombosis, cancer and recent progress in the different types of multivalent probes used to target selectins
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