Max Planck Society Background
Site-directed modification of proteins remains an important tool in biological research, medical engineering as well as the production of biopharmaceutical products and biosensors.
Currently, approaches based on interactions with His-tagged proteins have been developed. These are commonly adapted from the well-established purification technology utilising nickel (II)- mediated coordination of nitrilotriacetic acid (NTA) or iminodiacetic acid (IDA) with the imidazole groups of histidines.
Numerous applications such as the oriented immobilization of proteins on surfaces and the conjugation of fluorophores as well as other molecules to proteins are based on these [Ni(II)(NTA/IDA)(His-tag)] complexes. However, current methods come with major constrains such as low affinity and rapid ligand exchange rates of these complexes.
Scientists from the Max-Planck-Institute for Medical Research have developed a stable, site-specific and physiological system for protein conjugation by cobalt (III)-carbonate mediated functionalization of His-tagged proteins with nitrilotriacetic acid (NTA) or iminodiacetic acid (IDA) based reagents. In comparison to the use of metal (II)-NTA/IDA mediated interactions, the application of low-spin octahedral paramagnetic complexes of cobalt(III) results in a quasi-covalent complex formation that is chemically inert towards various chelators and reduction agents. The workflow for complex formation via [Co(III)(NTA)(CO3)]2- or [Co(III)(IDA)(CO3)(H2O)] – complex reagents obviates a H2O2-dependent oxidation step and therefore overcomes current limitations. This allows a simple and site-specific protein or antibody conjugation under physiological conditions within a reasonable time without compromising conjugate stability, function and protein binding efficacy.
Max Planck Innovation are looking for a collaboration partner to further develop this exciting project.