title: Synthesis of Polyester Dendritic Scaffolds for Biomedical Applications.
abstract: 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 with99mTc for molecular imaging applications. Efficient CuAAC coupling is achieved using an azide-functionalized triethylene glycol monomethyl ether (TEG-N3). Removal of copper from the DPA ligand is successfully performed on G1 and G2 dendrimers prior to radiolabeling with99mTc. Radiolabeling of the G3 dendrimer is accomplished via transmetallation of the [CuDPA]2+ligand with99mTc, 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.
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4M1, Canada.
authors.forename: Lukas P
authors.initials: LP
authors.lastname: Sadowski
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4M1, Canada.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Edem
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4M1, Canada. valliant@mcmaster.ca.
authors.forename: John F
authors.initials: JF
authors.lastname: Valliant
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4M1, Canada. adronov@mcmaster.ca.
authors.forename: Alex
authors.initials: A
authors.lastname: Adronov
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; D011091:Polyesters
keywords: cathepsin B; click coupling; diagnostic imaging