Sialyl chemoenzymatic synthesis

Unverzagt, C., Chemoenzymatic synthesis of a sialylated undecasaccharide-asparagine... 

George, S. K. Schwientek, T Holm, B. Reis, C. A. Clausen, H. Kihlberg, J. Chemoenzymatic Synthesis of Sialylated Glycopeptides Derived from Mucins and T-Cell Stimulating Peptides. J. Am. Chem. Soc. 2001, 123, 11117-11125. 

A chemoenzymatic synthesis of di-, tetra-, and octavalent sialyl Lewis X ligands scaffolded on dendrimers has been reported (Scheme 67). 508 Hypervalent L-lysine cores with covalently attached 2-acetamido-2-deoxy-D-glucose residues were chemically prepared and enzymatically transformed into sialyl Lewis X-containing dendrimers using (3-(l— 4) ga-... 

Unverzagt, C. (1996) Chemoenzymatic synthesis of a sialylated undecasaccharide-asparagine conjugate. Angew. Chem. Int. Ed. 35,2350-2353. 

George SK, Schwientek T, Holm B, Reis CA, Clausen H, Kihlberg J, Chemoenzymatic synthesis of sialylated glycopeptides derived from mucins and T-cell stimulating peptides, J. Am. Chem. Soc., 123(45) 11117-25, 2001. 

Schmidt D, Sauerbrei B, Thiem J. Chemoenzymatic synthesis of sialyl oligosaccharides with sialidases employing transglycosylation methodology. J. Org. Chem. 2000 65 8518-8526. 

Kondo, H, Ichikawa, Y, Wong, C-H, (i-Sialyl phosphite and phosphoramidite synthesis and application to the chemoenzymatic synthesis of CMP-sialic acid and sialyl oligosaccharides, J. Am. Chem. Soc., 114, 8748-8750, 1992. 

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... 

Fig. 10) [165], The Cytel corporation in San Diego has been able to scale-up this process for the routine production of kilogram quantities in each run of reactions [144]. The sialyl Le tetrasaccharide and its analogs are of pharmaceutical interest in the context of new treatments for chronic inflammatory diseases (psoriasis, rheumatoid arthritis), tumors, and tissue injuries following a heart attack, stroke, or organ transplant. Sialyl Lex and its analogs are therefore enthusiastically pursued by several pharmaceutical companies. Strategies for the solid-phase chemoenzymatic synthesis of glycopeptides (and glycolipids) containing sialyl Lex have also been designed and reported [144,156, and references therein].

The Sialyl Lewis Group and its Analogues as Ligands for Selectins Chemoenzymatic Synthesis and Biological Functions... 

V. Wittmann, A. K. Datta, K. M. Koeller, and C.-H. Wong, Chemoenzymatic synthesis and fluorescent visualization of cell-surface selectin bound sialyl Lewis X derivatives, Chem. Eur. J., 6 (2000) 162-171. 

C. Unverzagt, Chemoenzymatic synthesis of a sialylated diantennary V-glycan linked to asparagine, Carbohydr. Res., 305 (1998) 423 31. 

Chemoenzymatic Synthesis of Lactosamine and (a2—>3)Sialylated Lactosamine Building Blocks... 

Scheme 10. Chemoenzymatic synthesis of sialylated lactosamine with N-phthalimide as N protecting group.

Scheme 13. Chemoenzymatic synthesis of N-Trocprotected sialylated lactosamine donor 34. CMP-NeuSAc synthetase (29) and Neu5Ac(a2- 3)transferase (30) are known enzymes.

X. (2011) Efficient chemoenzymatic synthesis of sialyl Tn-antigens and derivatives. Chem. Commun. (Cambridge. U.K.), 47, 8691 8693. 

Scheme 3 Chemoenzymatic synthesis of sialyl lactose trisaccharide with C8 modifications...

A strategy of chemoenzymatic synthesis of C8-modified sialic acid analogues was recently reported by Withers and co-workers (Scheme 3) [83], The C8-modified sialic acid precursors 8-11 were synthesized from compounds 5-7, and each was converted to its CMP donor using a bacterial CMP-sialic acid synthetase. The Cst-1, an a 2,3-sialylatransferase from Campylobacter jejuni, was then selected and successfully used for the synthesis of sialyl thiolactoside 12-15. Notably, Cst-1 was shown to be more desirable for the synthesis of C8-modified sialyl lactose in comparison with another sialyltransferase PM0188h, which exhibited more hydrolysis activity toward natural substrates. 

Chemoenzymatic solution- and solid-phase synthesis of O-glycopeptides of the mucin domain of MAdCAM-1. A general route to O-LacNAc, O-sialyl-LacNAc, and O-sialyl-Lewis-X peptides, J. Am. Chem. Soc., 119 (1997) 8766-8776. 

S. Hanashima, S. Manabe, and Y. Ito, Divergent synthesis of sialylated glycan chains Combined use of polymer support, resin capture-release, and chemoenzymatic strategies, Angew Chem. Int. Ed., 44 (2005) 4218 1228. 

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