title: New sialyl Lewis(x) mimic containing an alpha-substituted beta(3)-amino acid spacer.
abstract: A highly convergent and efficient synthesis of a new sialyl Lewis(x) (sLe(x)) mimic, which was predicted by computational studies to fulfil the spacial requirements for a selectin antagonist, has been developed. With a beta(2,3)-amino acid residue l-galactose (bioisostere of the l-fucose moiety present in the natural sLe(x)) and succinate are linked, leading to a mimic of sLe(x) that contains all the required pharmacophores, namely the 3- and 4-hydroxy group of l-fucose, the 4- and 6-hydroxy group of d-galactose and the carboxylic acid of N-acetylneuraminic acid. The key step of the synthesis involves a tandem reaction consisting of a N-deprotection and a suitable O-->N intramolecular acyl migration reaction which is promoted by cerium ammonium nitrate (CAN). Finally, the new sialyl Lewis(x) mimic was biologically evaluated in a competitive binding assay.
authors.affiliation: Dipartimento di Chimica Organica e Biochimica, Università di Napoli Federico II, Via Cynthia, 4 I-80126 Napoli, Italy. pedatell@unina.it
authors.forename: Silvana
authors.initials: S
authors.lastname: Pedatella
authors.forename: Mauro
authors.initials: M
authors.lastname: De Nisco
authors.forename: Beat
authors.initials: B
authors.lastname: Ernst
authors.forename: Annalisa
authors.initials: A
authors.lastname: Guaragna
authors.forename: Beatrice
authors.initials: B
authors.lastname: Wagner
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palumbo
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001667:Binding, Competitive; D003432:Cross-Linking Reagents; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen
chemical_list: D000596:Amino Acids; D003432:Cross-Linking Reagents; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen