Vanadium-proteins. Structure, binding, characterization and biological implications

A growing interest for vanadium complexes (VCs) concerns their possible use in medicine.1 In biological fluids VCs with pharmacological action may give several transformation processes, among which the formation of species with the bioligands of organism. In this context, the binding of VCs to proteins plays a crucial role in the processes of transport in organism and action mode,2 even if for years little progress has been made in this area due to the complexity of studying these systems with usual techniques. The interaction depends on several factors: the structure of VC in aqueous solution, the number of available sites in the metal fragment, its thermodynamic stability, the presence of accessible residues on the protein structure, the stabilization of the adduct by secondary interactions, such as hydrogen bonds or van der Waals contacts,3 making the description of these systems a demanding and stimulating challenge for the inorganic, bioinorganic and medicinal chemists. Both covalent and non-covalent interactions are possible, with Asp, Asn, Glu, Gln, His, Ser residues being involved in the first one and Asp, Asn, Glu, Gln, Arg, Cys and Lys in the second one, and with the binding of one or more metal moieties. In this communication, the binding of VCs with small proteins such as hen egg white lysozyme,4,5 myoglobin,6 ubiquitin,7 cytochrome c,8 ribonuclease A,9 or larger proteins like G-actin,10 human serum transferrin in the apo or holo form,11 human serum albumin,12 hemoglobin,11 and immunoglobulin G11 will be presented. It will be shownthat a complete characterization is possible through a multi-technique approach based on spectrometry (MS), spectroscopy (EPR), computation (docking, DFT and molecular dynamics methods) and X-ray crystallography. The biological implications of VC-protein binding will also be discussed.