Unveiling the Interaction of Vanadium Compounds with Human Serum Albumin by Using 1H STD NMR and Computational Docking Studies

摘要

The binding of the VV oxidation products of two vanadium(IV) compounds, [VO(dmpp)2] and [VO(maltolato)2],which have shown promising anti-diabetic properties, to humanserum albumin (HSA) in aqueous aerobic solution hasbeen studied by 1H saturation transfer difference (STD) NMRspectroscopy and computational docking studies. Group epitopemapping and docking simulations indicate a preferenceof HSA binding to the 1:1 [VO2(dmpp)(OH)(H2O)]– and 1:2[VO2(maltol)2]– vanadium(V) species. By using known HSAbinders, competition NMR experiments revealed that both complexes preferentially bind to drug site I. Docking simulationscarried out with HADDOCK together with restraints derivedfrom the STD results led to three-dimensional modelsthat are in agreement with the NMR spectroscopic data, providinguseful information on molecular interaction modes.These results indicate that the combination of STD NMR anddata-driven docking is a good tool for elucidating the interactionsin protein–vanadium compounds and thus for clarifyingthe mechanism of drug delivery as vanadium compoundshave shown potential therapeutic properties.