New sialyl Lewis(x) mimic containing an alpha-substituted beta(3)-amino acid spacer.
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.
Pedatella
Silvana
S
Dipartimento di Chimica Organica e Biochimica, Università di Napoli Federico II, Via Cynthia, 4 I-80126 Napoli, Italy. pedatell@unina.it
De Nisco
Mauro
M
Ernst
Beat
B
Guaragna
Annalisa
A
Wagner
Beatrice
B
Woods
Robert J
RJ
Palumbo
Giovanni
G
D000596:Amino Acids / Q000737:chemistry*; D001667:Binding, Competitive; D003432:Cross-Linking Reagents; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen
D000596:Amino Acids; D003432:Cross-Linking Reagents; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen