Synthesis and biological evaluation of mannose-6-phosphate-coated multivalent dendritic cluster glycosides

Abstract

The synthesis of multivalent dendritic cluster glycosides of mannopyranosyl-6-phosphate is presented. Poly(amido amine)-based dendrimers of 0.5–3.5 generations, containing carboxylic acid peripheral functionalities, were utilized so as to install 4, 8, 16 and 32 mannopyranosyl-6-phosphate residues at the peripheries of the dendrimers. Amide bond formation between an amine-tethered mannopyranosyl-6-phosphate monomer unit and carboxylic acid-functionalized dendrimers was conducted to synthesize the dendritic cluster glycosides. The constitutions of the Man-6-P-containing dendrimers were assessed by ¹H, ¹³C and ³¹P NMR spectroscopies and the sugar content analysis by a resorcinol assay. Preliminary biological studies with few newly synthesized Man-6-P-containing dendrimers showed that these compounds could bind the purified goat liver mannose 6-phopshate receptor (MPR 300) protein.