title: Ligand interactions with E-selectin. Identification of a new binding site for recognition of N-acyl aromatic glucosamine substituents of sialyl Lewis X.
abstract: Several N-acylglucosamine derivatives of sialyl Lewis X (1-3) were prepared using a combined chemical enzymatic approach and evaluated as an inhibitor of E-selectin-mediated cellular adhesion. Compounds with aromatic functionality, 1 and 2, were found to be 3-10 times more potent than the N-acetyl derivative (14) in an ELISA E-selectin cell adhesion assay. Conformational analysis with NMR indicated that the sialyl Lewis x domain of 1 retained the conformation of the N-acetyl derivative (14) despite the presence of the N-naphthamido group. The dramatic order of magnitude increase in potency of these monovalent structures can be utilized to design more potent selectin-based cell adhesion inhibitors.
authors.affiliation: Cytel Corporation, San Diego, California 92121, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Ramphal
authors.forename: M
authors.initials: M
authors.lastname: Hiroshige
authors.forename: B
authors.initials: B
authors.lastname: Lou
authors.forename: J J
authors.initials: JJ
authors.lastname: Gaudino
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: S M
authors.initials: SM
authors.lastname: Chen
authors.forename: L C
authors.initials: LC
authors.lastname: Chiang
authors.forename: F C
authors.initials: FC
authors.lastname: Gaeta
authors.forename: S A
authors.initials: SA
authors.lastname: DeFrees
mesh_terms: D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D019040:E-Selectin / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007983:Lewis Blood Group Antigens; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000080506:Sialyl Lewis X Antigen
chemical_list: D019040:E-Selectin; D007983:Lewis Blood Group Antigens; D008024:Ligands; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D005944:Glucosamine