Chemoenzymatic synthesis of dendritic sialyl Lewis(x).
Traditional structure activity relationship studies (SAR) have led to the development of numerous sialyl Lewis(x) analogs in the search for potential antiinflammatory agents. However, these methods do not take into account cluster or multivalent effects. Reported herein is the chemoenzymatic synthesis of di-, tetra-, and octa-valent sLe(x) ligands scaffolded on dendrimers. Hypervalent L-lysine cores with covalently attached 2-acetamido-2-deoxy-D-glucose (N-acetylglucosamine, GlcNAc) residues were chemically prepared and enzymatically transformed into sLe(x) containing dendrimers so that multivalency, and its role in selectin-sLe(x) interactions may be evaluated. This work constitutes another successful enzymatic synthesis of sLe(x) and represents the first example of GlcNAc elongation on a synthetic dendrimer scaffold. These sLe(x) dendrimers are currently being investigated as selectin antagonists.
Palcic
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MM
Department of Chemistry, University of Alberta, Edmonton, Canada.
Li
H
H
Zanini
D
D
Bhella
R S
RS
Roy
R
R
D000117:Acetylglucosamine / Q000737:chemistry; D000606:Amino Sugars / Q000737:chemistry; D002240:Carbohydrate Sequence; D005647:Fucosyltransferases; D005700:Galactosyltransferases / Q000378:metabolism; D006020:Glycopeptides / Q000138:chemical synthesis; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis*; D011107:Polylysine / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen; D012799:Sialyltransferases
D000606:Amino Sugars; D006020:Glycopeptides; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D011107:Polylysine; C000458:N-acetyllactosamine; D005647:Fucosyltransferases; D005700:Galactosyltransferases; D012799:Sialyltransferases; D000117:Acetylglucosamine