The synthesis of disaccharides for the functionalization of PAMAM dendrimers

Abstract

An increase in the number of incidences of fungal disease among immuno-compromised patients has developed in recent years. While a patient with an intact immune system would be able to fight the pathogen, an immunocompromised patient is not able to do so. The mortality rate of disseminated candidiasis can be as high as 30-40%. Although there have been great advances in the understanding of how the immune system detects pathogens, there is still much to be learned. PAMAM (poly(amidoamine)) dendrimers have been chosen as scaffolds on which to display disaccharides that are found on the surface of Candida albicans. Preliminary results from immunostimulation assays using a(1,2)-dimannose functionalized PAMAM dendrimers showed that disaccharide functionalized dendrimers can stimulate cytokine production. In light of these results, several disaccharides - phenyl 2-O-benzyl-4,6-O-benzylidene-3-O-(2,3,4,6-tetra-O-acetyl-a-D-mannopyranosyl)-1-thio-a-D-mannopyranoside, 1-O-2-(2-azidoethoxy)ethyl-3-O-benzyl-4,6-O-benzylidene-2-O-(2,3-di-O-benzyl-4,6-O-benzylidene-B-D-mannopyranosyl)-a-D-mannopyranoside, 1-O-2-(2-azidoethoxy)ethyl-3-O-benzyl-4,6-O-benzylidene-2-O-(2,3-di-O-benzyl-4,6-O-benzylidene-B-D-glucopyranosyl)-B-D-glucopyranoside, 1-O-2-(2-azidoethoxy)ethyl-2-O-benzyl-4,6-O-benzylidene-3-O-(2,3-di-O-benzyl-4,6-O-benzylidene-B-D-glucopyranosyl)-B-D-glucopyranoside - have been synthesized for the functionalization of G(3.5) PAMAM dendrimers.