Enzymatic synthesis of a sialyl Lewis X dimer from egg yolk as an inhibitor of E-selectin.
A dimeric sialyl Lewis X (SLex) glycopeptide was synthesized enzymatically in three steps from an N-linked oligosaccharide prepared from egg yolk. Treatment of delipidated hen egg yolk with the protease Orientase and neuraminidase gave a dimeric N-acetyllactosamine-containing oligosaccharide linked to asparagine. Addition of sialic acid and fucose catalyzed by alpha-2,3-sialyltransferase and alpha-1,3-fucosyltransferase provided the dimeric SLex, which was shown to be as active as monomeric SLex as an inhibitor of E-selectin with IC50 0.75 mM. The synthetic dimeric SLex of the mucin type (i.e. SLex linked to the 3- and 6-OH groups of Gal) is, however, about five times as active as the monomer. It is suggested that dimeric SLex glycopeptides of the mucin type would be effective ligands for E-selectin.
Lin
C H
CH
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Shimazaki
M
M
Wong
C H
CH
Koketsu
M
M
Juneja
L R
LR
Kim
M
M
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002645:Chickens; D019040:E-Selectin / Q000187:drug effects* / Q000378:metabolism; D004530:Egg Yolk / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology*; D000080506:Sialyl Lewis X Antigen
D019040:E-Selectin; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen