Synthesis and biological evaluation of a new sialyl Lewis X mimetic derived from lactose.
A sialyl Lewis X (sLe(x)) mimetic compound, 2-(trimethylsilyl)ethyl 3-O-carboxymethyl-beta-D-galactopyranosyl-(1-->4)-[alpha-L-fucosyl-(1-->6)]-beta-D-glucopyranoside (2a), has been synthesized in 14 steps from D-lactose. This synthesis features the use of the activated glycosylating donor, lactosyl iodide, in a Koenigs-Knorr sequence, the regioselective derivatization at the C-3 position of the galactose moiety, and the stereoselective construction of a fucose-alpha(1-->6)-lactose linkage. The mimetic was tested for its ability to inhibit human polymorphonuclear leukocyte (hPMNL) adhesion to immobilized recombinant human E-selectin under shear stress conditions.
Chervin
Stephanie M
SM
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.
Lowe
John B
JB
Koreeda
Masato
M
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007785:Lactose / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D000080506:Sialyl Lewis X Antigen; D013329:Structure-Activity Relationship
D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D007785:Lactose