The study of the binding between potential vanadium drugs and proteins is fundamental to determine their transport in the organism, speciation in blood and cytosol, pharmacological properties and mechanism of action. In this talk, an integrated instrumental/computational approach to characterize the interaction between vanadium species and proteins will be discussed. ElectroSpray Ionization-Mass Spectrometry allows determining the number of moieties (VIVO2+/VIVOL/VIVOL2/VIVL2 or VVO2+/VVO2L/VVO2L2) bound to proteins, EPR distinguishing the type of residues involved in the coordination of VIV moieties, docking/DFT/QM/MM methods predicting the specific residues involved in the binding and stabilization of the structure through secondary bonds such hydrogen and van der Waals bonds, and X-ray diffraction analysis, when possible, ascertaining the complete 3D structure of the adducts. The interaction of VIV/V complexes with various proteins, such as transferrin, albumin, immunoglobulin G, hemoglobin, lysozyme, myoglobin, ubiquitin, cytochrome c and ribonuclease A will be presented. Moreover, both covalent and non-covalent binding will be reviewed and related to the type of metal moieties existing in aqueous solution. Finally, the implications of these results in the speciation of vanadium drugs and their interconversion in the biological fluids will be discussed as well as in a rational design of new vanadium drugs and interpretation of their biological action.
Integrated instrumental/computational methods to characterize the binding to proteins and biospeciation of potential vanadium drugs
Daniele Sanna;Valeria Ugone;
2021
Abstract
The study of the binding between potential vanadium drugs and proteins is fundamental to determine their transport in the organism, speciation in blood and cytosol, pharmacological properties and mechanism of action. In this talk, an integrated instrumental/computational approach to characterize the interaction between vanadium species and proteins will be discussed. ElectroSpray Ionization-Mass Spectrometry allows determining the number of moieties (VIVO2+/VIVOL/VIVOL2/VIVL2 or VVO2+/VVO2L/VVO2L2) bound to proteins, EPR distinguishing the type of residues involved in the coordination of VIV moieties, docking/DFT/QM/MM methods predicting the specific residues involved in the binding and stabilization of the structure through secondary bonds such hydrogen and van der Waals bonds, and X-ray diffraction analysis, when possible, ascertaining the complete 3D structure of the adducts. The interaction of VIV/V complexes with various proteins, such as transferrin, albumin, immunoglobulin G, hemoglobin, lysozyme, myoglobin, ubiquitin, cytochrome c and ribonuclease A will be presented. Moreover, both covalent and non-covalent binding will be reviewed and related to the type of metal moieties existing in aqueous solution. Finally, the implications of these results in the speciation of vanadium drugs and their interconversion in the biological fluids will be discussed as well as in a rational design of new vanadium drugs and interpretation of their biological action.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
