Development of an universal affinity fusion tag (Poly‐DOPA) for immobilizing recombinant proteins on biomaterials

The covalent and non‐covalent immobilization of growth factors such as recombinant human bone morphogenetic protein 2 (rhBMP‐2) on metals and bone replacement materials in bioactive form is a recent development. Up to now the immobilization technology usually involved the chemical modification and activation of the biomaterial surface followed by attachment of the bioactive protein. Here we suggest an alternative method in which an affinity tag fused to an active protein will allow immobilization without additional chemistry. For biomaterials such as minerals, metals (titanium, steel, CoCrMo), glass ceramics, teflon and possibly bone and teeth ideal adhesion molecules would be the foot proteins (Mefps) of the mussel M. edulis which contain the rare amino acid dihydroxy phenylalanine (DOPA). Recently it could be shown by Messersmith's group that a single DOPA‐molecule can be non‐covalently bound to titanium dioxide surface with a dissociation energy of 22.2 kcal/mol (Lee, H.; Scherer, N. F.; Messersmith, P. B. Proc. Natl. Acad. Sci. U. S. A 2006, 103, 12999–13003).We therefore propose the DOPA‐tag as a general and versatile affinity tag for the immobilization of proteins on biomaterials.