A facile synthetic approach to L- and P-selectin blockers via copolymerization of vinyl monomers constructing the key carbohydrate modules of sialyl LewisX mimics.
A highly practical synthetic approach is described for artificial L- and P-selectin blockers. The synthesis involves radical bi- and terpolymerizations of p-(N-acrylamido)phenyl 3- or/and 6-sulfo-beta-D-galactoside with allyl alpha-L-fucoside in the presence of acrylamide. Each of the two glycosyl monomers constructs a key carbohydrate module responsible for selectins/sulfated sialyl LewisX (sLeX) bindings. Whereas an acrylamide copolymer carrying 3-sulfo-galactoside showed no activity for any selectins, the fucosylated terpolymer showed a potent activity to block both of P- and L-selectins/sLeX binding at a concentration of a few micrograms per milliliter. The enhanced activity is apparently ascribed to the cooperative binding effects of the fucoside and the 3-sulfo-galactoside residues.
Nishida
Y
Y
Department of Molecular Design, Department of Biotechnology, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan.
Uzawa
H
H
Toba
T
T
Sasaki
K
K
Kondo
H
H
Kobayashi
K
K
D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000138:chemical synthesis* / Q000494:pharmacology; D005643:Fucose / Q000737:chemistry; D007202:Indicators and Reagents; D019041:L-Selectin / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D019007:P-Selectin / Q000378:metabolism*; D011108:Polymers / Q000138:chemical synthesis; D000080506:Sialyl Lewis X Antigen; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D002241:Carbohydrates; D007202:Indicators and Reagents; D009844:Oligosaccharides; D019007:P-Selectin; D011108:Polymers; D000080506:Sialyl Lewis X Antigen; D014753:Vinyl Compounds; D019041:L-Selectin; D005643:Fucose