Selectin-carbohydrate interactions selectins

Lasky, L. A., 1995. Selectin-carbohydrate interactions and the initiation of die inflammatory response. Annual Review of Biochemistry 64 113-139. 

McEver, R.P., Moore, K.L., Cummings, R.D. (1995) Leukocyte trafficking mediated by selectin-carbohydrate interactions. 

Sanders WJ, Katsumoto TR, Bertozzi CR, Rosen SD, Kiessling LL. L-selectin-carbohydrate interactions relevant modifications of the Lewis x trisaccharide. Biochemistry 1996 35 14862-14867. 

The selectins are a family of lectins that mediate the movement of leukocytes from the bloodstream into sites of inflammation. This multistep cascade proceeds by initial attachment leading to the rolling of leukoc)rtes along endothelial vasculature via selectin-carbohydrate interactions. Subsequent firm adhesion requires chemoattractant activation of leukocyte p2 integrins which mediate arrest through interaction with endothelial receptors. Leukocytes then extravasate between endothelial cells in the direction of chemoattractants as indicated in O Fig. 3 [42]. 

The SLe epitope is expressed on inflammation-induced acute phase proteins which serve as endogenous competitors for selectins and mediate a dampening of the immune response, returning inflammation to homeostasis [53]. Inhibitors of the selectins have been proposed to be useful therapies for treating inflammatory disorders including respiratory distress [54], hypersensitivity responses [55], and surgically induced myocardial ischemic reperfusion injury [56]. Animal studies have shown that the inhibition of selectin-carbohydrate interactions can alleviate these inflammatory responses. 

McEver, R.P. (1997) Selectin-carbohydrate interactions during inflammation and metastasis. Glycoconjugate Journal, 14, 585-591. 

Experimental Systems for Studies of Selectin-Carbohydrate Interactions. 249... 

Many of the individual topics addressed in the present chapter have been discussed in the context of excellent specialist reviews. Some of these are cited in the respective sections. Wong and his associates have prepared a comprehensive review entitled Selectin-Carbohydrate Interactions from Natural Ligands to Designed Mimics which provides a complete survey of the literature dealing especially with the medicinal chemistiy aspects of selectin inhibitor design treatment of this aspect has therefore been restricted to a few representative examples in the present article. Vcstwcbcr has edited a comprehensive monograph entitled The Selectins Initiators of Leukocyte Endothelial Adhesion. 

Fig. 8. Distribution of selectins and their glycoprotein ligands. Reprinted with permission from Rodger P. McEver, Selectin-carbohydrate interactions during inflammation and metastasis, Glycoconjugate J.. 14 (1997) 585-591 (Ref. 208) (1997). Kluwer Academic Publishers.

V Approaches to Pharmaceutically Applicable Inhibitors OF Selectin-Carbohydrate Interactions... 

Many of these techniques have also been successfully utilized for the identification of inhibitors of protein-carbohydrate interactions. ELIS As are often employed, and their utility is illustrated in the efforts to identify selectin inhibitors [51-53]. However, other assays such as fluorescence polarization [33, 54] and carbohydrate affinity matrices [55] have also been utilized. These methods have provided valuable information about the substrate specificity of a number of carbohydrate-binding proteins and led to the discovery of many useful inhibitors. Still, there remains an acute need to develop effective high-throughput assays. 

E.E. Simanek, G.J. McGarvey, J.A. Jablonowski, C.-H. Wong, Selectin-carbohydrate interactions from natural ligands to designed mimics, Chem. Rev. 1998, 98, 833-862. 

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