Synthesis and biological evaluation of α-D-mannopyranoside-containing dendrimers

Abstract

The extension of dendritic synthetic principles to the preparation of new kinds of dendrimer-based glycoconjugate systems has been investigated. A convergent growth approach to the synthesis of α-d-mannopyranoside-containing dendrimers of various generations has been used successfully to obtain high molecular weight and monodisperse dendrimers in which 3-36 identical copies of the mannopyranoside residues are located at their peripheries. A repetitive synthetic sequence for forming amide bonds is employed in the preparation of various dendritic wedges and their attachment to a 1,3,5-trisubstituted benzenoid core in the last step. The protecting groups on the saccharide residues are then finally removed to obtain free saccharide-containing dendrimers. The efficacy of these dendrimers in inhibiting the binding of concanavalin A lectin to a purified yeast mannan fraction (as measured by an enzyme-linked lectin assay) is shown to be about four times more pronounced on a molar basis for the dendrimers possessing nine, 18, and 36 mannose residues, when compared to a dendritic wedge possessing three mannose residues and methyl α-d-mannopyranoside as control inhibitors.