Polyphenylene dendrimers as scaffolds for shape-persistent multiple peptide conjugates

The present work describes synthetic concepts for the coupling of peptides to polyphenylene dendrimers (PPDs). Novel functionalized cyclopentadienones have been synthesized whose Diels-Alder cycloaddition with various core molecules leads to polyphenylene dendrimers possessing (protected) amino or carboxyl groups. In addition, the resulting functionalized molecules exhibit the characteristic shape-persistence and monodispersity of PPDs. Their functions have been used for the attachment of polylysine to the dendritic scaffold. Three different methods for the decoration of dendrimers with polypeptides are presented. First, polylysine segments are grafted from the surface of the dendrimers employing α-amino acid N-carboxyanhydride (NCA) polymerization. Second, the C-terminal carboxyl groups of protected polypeptides are activated and then coupled to the amino groups on the surface of the PPD. Finally, cysteine terminated, unprotected peptide sequences are attached to polyphenylene dendrimers utilizing the addition of the sulfhydryl group of a cysteine to the maleimide functions on the dendrimer surface. Moreover, Diels-Alder cycloaddition of suitably functionalized cyclopentadienons to a desymmetized core molecule allows the design of a dendritic scaffold with a specific number of different anchor groups on its periphery. These approaches are important for the tailoring of new, shape-persistent, polyfunctional multiple antigen conjugates. © 2005 American Chemical Society.