Synthesis of dicarboxylate oligosaccharide multilayer terminal functionality upon poly(lysine) dendrimer scaffolding

A reactive three-layered dendrimer containing carboxyl groups was synthesized by the coupling of dicarboxylic acid and a highly reactive, two-layered glycopeptide dendrimer. Lactose, maltose, or maltotriose was reacted with the poly(lysine) dendrimer in its third and fourth generations by reductive amination and afforded two-layered glycolysine dendrimers. The reaction was conducted in a borate buffer (pH 9.0). H-1 NMR, C-13 NMR, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analyses were applied for the determination of the structures of the products. When an excess amount of the oligosaccharide and a long reaction time were used, the degree of substitution increased to 1.5-2.0 against an amino group. For the preparation of highly reactive, multilayered dendrimers for an antigen carrier, C6 hydroxy groups of the oligosaccharides were selectively esterified by adipic acid and suberic acid to give 6-O-adipoyl oligosaccharide-poly(lysine) dendrimers and 6-O-suberoyl oligosaccharide-poly(lysine) dendrimers. The reactivity of these multilayered dendrimers was examined by a model reaction with phenylalanine ethyl ester. The dendrimer showed high reactivity, providing phenylalanine ethyl ester-dicarboxylate oligosaccharide-poly(lysine) dendrimers with a considerably high proportion of phenylalanine residues. (C) 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3622-3633, 2002.