Synthesis and protein binding properties of T-antigen containing GlycoPAMAM dendrimers

Allyl O-(beta-D-galactopyranosyl)-(1-3)-2-acetamido-2-deoxy-alpha-D-galactopyranoside (8) was prepared in excellent yield from the corresponding galactosyl bromide (6, 7) and allyl 2-acetamido-4,6-benzylidene-2-deoxy-alpha-D-galactopyranoside (5) using Hg(CN)2 as a promoter. Compound 5 was obtained from N-acetylglucosamine 1 following sequential protecting group strategy and C-4 epimerization as a key step. Carboxylic acid functionalized T-antigen derivative 15, obtained by radical addition of 3-mercaptopropionic acid to allyl disaccharide 10, was conjugated to PAMAM dendritic cores 13-16 by an efficient amide coupling strategy using TBTU. GlycoPAMAM dendrimers having T-antigen residues with 4, 8, 16 and 32 valencies (17-20) were obtained in 73 to 99% yields. Their protein binding properties were demonstrated using peanut lectin from Arachis hypogaea and a mouse monoclonal IgG antibody. The higher valency conjugates generated stronger binding interactions indicating a cluster effect. The inhibitory potential of these glycoPAMAM conjugates toward antibody-coating antigen interactions was enhanced up to 3800 times over that of the monomeric T-antigen residue (10).