Synthesis of biologically active sialyl Lewis X mimetics

Article abstract of DOI:10.1021/jo00115a027

The design and synthesis of two sialyl Lewis X (SLe(x)) mimetics are described. In the design of mimetic 1, an ethylene glycol linkage is used to bridge the fucose and galactose moiety, and a carboxymethyl group is placed in the 3-OH position of the galactose residue to provide the negative charge which is believed to be essential for binding to (E)-selectin. In the design of mimetic 2, a D-tartaric acid derivative is used to provide the trans-dihydroxyl groups originally from the glucosamine moiety for the linkage of the fucose and the carboxypentyl groups. At a concentration of 1.5 mM, 1 inhibits 50% of the binding of SLe(x) glycoconjugate to immobilized recombinant (E)-selectin, while 2 has an IC₅₀ of 10 mM. Mimetic 1 is also found to be stable toward α-L-fucosidase. Results from the ROESY and COSY experiments indicate that compound 1 is conformationally flexible, which may explain its relatively weak activity compared to SLe(x) (IC₅₀ = 0.8 mM).