Synthesis of Polyester Dendritic Scaffolds for Biomedical Applications

Using a well-defined poly(2,2-bis(hydroxymethyl)propanoic acid) dendrimer scaffold, a series of G1 to G3 dendrons is functionalized at the periphery with alkynes to enable Click functionalization via the copper-catalyzed alkyne-azide cycloaddition (CuAAC). The resulting dendrons are further functionalized at the core with a dipicolylamine (DPA) moiety to enable radiolabeling with Tc-99m for molecular imaging applications. Efficient CuAAC coupling is achieved using an azide-functionalized triethylene glycol monomethyl ether (TEG-N-3). Removal of copper from the DPA ligand is successfully performed on G1 and G2 dendrimers prior to radiolabeling with Tc-99m. Radiolabeling of the G3 dendrimer is accomplished via transmetallation of the [CuDPA](2+) ligand with Tc-99m, further demonstrating the feasibility of the synthetic strategies in the preparation of dendritic imaging agents. Subsequent attachment of an acyloxymethyl ketone (AOMK) derivative for targeting of cathepsin B is also explored. Despite demonstrating the ability to ligate multiple AOMK ligands, the AOMK-dendrimer conjugates are not able to bind to cathepsin B, which may be attributed to steric hindrance at the dendrimer periphery.