Sialyl Lewisx

G.E.R. Weller, F.S. Villanueva, E.M. Tom, W.R. Wagner, Targeted ultrasound contrast agents In vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl Lewisx, Biotechnol. Bioeng. 92 (2005) 780-788. 

Zanini D, Roy R (1996) Chemo-enzymatic synthesis of multivalent N-acetyllactosamine compounds as dendritic sialyl LewisX precursors. Proceedings of the XVIlIth International Carbohydrate Symposium, Milan, Italy, Juli 21 -26, p 236 Pag6 D, Zanini, D, Roy R (1996) Bioorg Med Chem 4 1949 Roy R, Baek MG, Zanini D, (unpublished data)... 

Other glycopolymers carrying a sialyl Lewisx mimic were obtained by copolymerization of functionalized carbohydrate monomers with acrylamide for... 

In one recent example of the traditional procedure, monomeric and dimeric sialyl Lewisx-type molecules, that are implicated in leukocyte inflammation, have been synthesized in a highly regioselective manner using mercury salts as catalysts250,251. 

Schermerhorn ML, Nelson DP, Blume ED, Phillips L, Mayer JE Jr. Sialyl LewisX oligosaccharide preserves myocardial and endothelial function during cardioplegic ischemia. Ann. Thorac. Surg. 2000 70 890-894. 

Recombinant human FucT VI [84, 85] (EMBL accession no. L01698) has been used to synthesize sialyl-Lewisx and a number of related tetrasaccharides. In vivo, the enzyme transfers a fucose unit from GDP-Fuc [42] onto the 3-OH group of a GlcNAc moiety in an a-mode (Fig. 10). 

When an N-acetyllactosamine acceptor is fucosylated Lewisx is obtained. If the terminal galactose of the N-acetyllactosamine acceptor carries a sialic acid, the fucosylation of the AT-acetylglucosamine unit leads to sialyl-Lewisx (as depicted in Fig. 10) [86, 87]. In consequence, this means that the 3-OH group of... 

A number of non-natural fucosyl donors have also been probed with this enzyme [89]. As can be seen from Fig. 12, the C-6-atom of fucose is open for modifications. L-Gal and D-Ara are good substrates, whereas replacement of the 2-OH group of the fucose donor apparently is not tolerated by FucT VI. Indeed, Hindsgaul and coworkers succeeded in attaching the blood group A trisaccharide to the 6-position of the fucose donor and proved the biocatalytic transfer of this strange sugar [90]. The combination of non-natural donors with non-natural acceptors by enzymatic fucosyltransfer has also been probed which proved to be instrumental in the assembly of a library of sialyl-Lewisx tetrasaccharides (Fig. 12) [91]. 

Since sialic acid and fucose are important in the binding interaction of sialyl Lewisx to the selectins,45-50 a reasonable conjecture is that removal of fucose from sialyl Lewisx will completely stop the binding of leukocytes to the endothelium. Furthermore, this may be accomplished by inhibiting the activity of a-l,3-fucosyltransferase thus preventing the formation of sialyl Lewisx. 

Interaction between the glycoprotein E-selectin (expressed on the surface of endothelial cells) and the sialyl Lewis 1 ligand structures on the surface of neutrophils is a major event in inflammation, infection, and metastasis. Both chemical and enzymatic syntheses have been described for the synthesis of the sialyl Lewisx structure. A summary of the general strategy used in chemoenzymatic synthesis is shown here. Extensive in situ regenerations of the sugar nucleotides are not shown in the scheme.97... 

Multistep enzymatic transformations can be done with combinations of compatible aldolases, glycosyltransferases and recycling systems. A practical and successful example for this concept is the multienzymatic synthesis of the sialyl Lewisx tetrasaccharide (sialyl Le ... 

E. Grabenhorst, M. Nimtz, J. Costa, H. S. Conradt, In vivo specificity of human alphal,3/4-fucosyltransferases III-VII in the biosynthesis of LewisX and sialyl LewisX motifs on complex-type N- glycans. Coexpression studies from Bhk-21 cells together with human beta-trace protein, J Biol Chem, (1998), 273, 30985-94. 

Gege, C. Oscarson, S. Schmidt, R. R. Synthesis of fluorescence labeled sialyl Lewisx glycosphingolipids. Tetrahedron Lett. 2001, 42, 377-380. 

Linden, ECMV Haan, PF Havenaar, EC van Dijk, W. Inflammation-induced expression of sialyl Lewisx is not restricted to Glycoconjugate Journal, 1998, 15, 177-82. 

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