Sialyl Lewis’1

Flgure10.23 Sialyl Lewis -related selectin inhibitorandfluorogenicscreening compound for transketolase prepared using enzymatic aldolization, and multienzymatic oxidation-aldolization strategy for the synthesis of bicyclic higher carbon sugars. 

Fluorogenic compound (56) for transketolase assays has been prepared making use of FruA specificity [123]. Pendant anionically charged chains have been extended from O- or C-glycosidic aldehydes to furnish low molecular weight mimics of the sialyl Lewis X tetrasaccharide such as (SS) (Figure 10.23) [124], Other higher carbon... 

Selectins L-selectin PMN, lymphs CD34,Gly-CAM-L Sialyl-Lewis" and others... 

The precise chemical nature of some of the ligands involved in selectin-ligand interactions has been determined. All three selectins bind sialylated and fucosy-lated oligosaccharides, and in particular all three bind sialyl-Lewis (Figure 47-12), a structure present on both glycoproteins and glycolipids. Whether this compound is the actual ligand involved in vivo is not estab-... 

Figure 47-12. Schematic representation of the structure of sialyl-lewis . ...

SLE Systemic lupus erythematosus SLe Sialyl Lewis X antigen SLO Streptolysin-O SLPI Secretory leucocyte protease inhibitor... 

Yang W, Fan H, Gao X et al (2004) The first fluorescent diboronic acid sensor specific for hepatocellular carcinoma cells expressing sialyl Lewis X. Chem Biol 11 439 148... 

T. Furiuke, R. Sadamoto, K. Niikura, K. Monde, N. Sakairi, and S.-I. Nishimura, Chemical and enzymatic synthesis of glycocluster having seven sialyl lewis X arrays using /i-cyclodextrin as a key scaffold material, Tetrahedron, 61 (2005) 1737-1742. 

Scheme 8.1 Synthesis of a sialyl-Lewis tetrasaccharide employing C-enriched protecting groups for the quantitative reaction monitoring using gated decoupling NMR spectroscopy.

N-Glycopeptides Carrying the Sialyl Lewis A Structure The regioisomeric tetrasaccharide structures sialyl Lewis A (sLea) (NeuAca(2—>3)Galp( 1 —>3) [Fuca(l— 4)]GlcNAc) and sialyl Lewis X (sLex)50 (NeuAca(2—>3)Galp( 1 —>4)... 

Scheme 13.14 Synthesis of a sialyl Lewis A buiding block for solid-phase glycopeptide synthesis.

Scheme 13.15 Solid-phase synthesis of a sequence from PSGL-1 carrying sialyl-Lewis A.

A similar approach was used in the synthesis of the sialyl Lewis X mimetics of type 85 (Scheme 13.22).66 Protein crystallization,67 conformational studies of sLex in solution68 and in bound form to E- and P-selectin69 as well as the study of structure-function relationships70,71 gave information about the functional groups of the sLex-epitope essential for the binding to the selectins. Synthesized mimetics must contain the three essential hydroxyl functions of the fucose. Sialic acid, galactose, and... 

PfPyU—V,V-A A -bis(tetramethylene)-C>-pentafluorophenyluroniumhexafluorophosphat Pmc—2,2,5,7,8-pentamethyl-chromane-6-sulfonyl SLe37 —sialyl Lewis A/X... 

Selectins mediate contact by binding to carbohydrate-containing receptors on leucocytes through their N-terminal lectin domain. Sialyl-Lewis X (Neu5Aca2-3-Gaipi-4(Fucal-3)Glc-NAc) and derivatives thereof were shown to bind to the selectins and subsequently inhibit ischaemia-induced leucocyte infiltration in the liver [76-78]. A similar compound prevented antigen-induced late bronchial responses and airway hyper-responsiveness in allergic sheep [79]. 

The binding potency of the native sialyl-Lewis X can be increased with three orders of magnitudes by conjugating this saccharide to BSA. This is probably due to the clustering of saccharides that may favour binding to E-selectin [80]. 

Carrel F, Giraud S, Spertini O, Vogel P (2005) New non-hydrolyzable mimetics of sialyl Lewis x and their binding affinity to P-selection. Helv Chim Acta 87 1048-1070... 

Using the same procedure, the synthesis of the thiogalabioside (87b) was reported very recently [54]. Also, this year an orthogonal synthesis of a thio-linked analogue of the sialyl Lewis X (93) has been described using known coupling reactions (Scheme 26) [55]. 

The same group recently reported the chemical synthesis of sialyl-Lewis X and A epitope analogues containing the N-methyl derivative of (33) [87]. 

S- [51], and C- [49,52] a-sialosides have been prepared using copolymerization or grafting methods. More complex sialylohgosaccharide-containing polymers have also been prepared, including GM3 [53], sialyl Lewis [54], sialyl Lewis [55], and a related 3 -sulfo-Lewis analog [56, 57], including polymerized liposomes [58]. 

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