An investigation of the interactions of E-selectin with fuco-oligosaccharides of the blood group family.
This investigation is concerned with assignments of Lewis(a) (Le(a)) and Le(x) analogs on linear and branched di- to hexasaccharide backbones as components of the recognition motifs for E-selectin. The influence of the location of fucose residue(s) was investigated using 14 structurally defined and variously fucosylated oligosaccharides in biotinylated form or as neoglycolipids in static binding assays, in microwells, and on thin-layer chromatograms. Results of the two assay systems were in agreement overall and showed that the recognition motifs for E-selectin include 4-fucosyl-lacto (Le(a)) and 3-fucosyl-neo-lacto (Le(x)) sequences strictly at capping positions and not Le(x) at an internal position as a part of VIM-2 antigen sequence. There is greater potency of the Le(a) over the Le(x) series. Additional fucose residues alpha1-2-linked to neighboring galactoses or alpha1-3-linked to inner N-acetyglucosamines or to reducing-terminal glucose residues of the tetrasaccharide backbone had little or no effect on the selectin binding. E-selectin binding to the Le(a) or Le(x )capping motif on a 3-linked branch was equivalent to the binding on the corresponding linear backbone. A lack of E-selectin binding to the Le(x) motif capping a 6-linked branch and to the Le(x) trisaccharide linked to biotin via a nine-carbon spacer indicates that the -GlcNAcbeta1-3Gal- sequence on the oligosaccharide backbone adjoining the Le(x) is a part of recognition motif for E-selectin. These findings contribute to understanding the molecular basis of E-selectin recognition and could influence future designs of selectin antagonists as possible therapeutic substances.
Martín
María J
MJ
Imperial College School of Medicine, Northwick Park Campus, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom.
Feizi
Ten
T
Leteux
Christine
C
Pavlovic
Davor
D
Piskarev
Vladimir E
VE
Chai
Wengang
W
D001665:Binding Sites; D001789:Blood Group Antigens / Q000097:blood* / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D019040:E-Selectin / Q000097:blood*; D005643:Fucose / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000097:blood*
D001789:Blood Group Antigens; D019040:E-Selectin; D009844:Oligosaccharides; D005643:Fucose