TY - JOUR
T1 - Unveiling the interaction of vanadium compounds with human serum albumin by using 1H STD NMR and computational docking studies
AU - Dias, David M.
AU - Rodrigues, João P.G.L.M.
AU - Domingues, Neuza S.
AU - Bonvin, Alexandre M.J.J.
AU - Castro, M. Margarida C.A.
PY - 2013/9
Y1 - 2013/9
N2 - 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 human serum albumin (HSA) in aqueous aerobic solution has been studied by 1H saturation transfer difference (STD) NMR spectroscopy and computational docking studies. Group epitope mapping and docking simulations indicate a preference of HSA binding to the 1:1 [VO2(dmpp)(OH)(H2O)]- and 1:2 [VO 2(maltol)2]- vanadium(V) species. By using known HSA binders, competition NMR experiments revealed that both complexes preferentially bind to drug site I. Docking simulations carried out with HADDOCK together with restraints derived from the STD results led to three-dimensional models that are in agreement with the NMR spectroscopic data, providing useful information on molecular interaction modes. These results indicate that the combination of STD NMR and data-driven docking is a good tool for elucidating the interactions in protein-vanadium compounds and thus for clarifying the mechanism of drug delivery as vanadium compounds have shown potential therapeutic properties. 1H STD NMR analysis complemented by HADDOCK studies have revealed that the [VO2(dmpp)(H2O)(OH)] - species, resulting from the oxidation of the potential insulin mimetic VO(dmpp)2, binds preferentially to HSA site I. These findings corroborate the involvement of this serum protein in the transport of vanadium species in the blood stream and their delivery to target cells.
AB - 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 human serum albumin (HSA) in aqueous aerobic solution has been studied by 1H saturation transfer difference (STD) NMR spectroscopy and computational docking studies. Group epitope mapping and docking simulations indicate a preference of HSA binding to the 1:1 [VO2(dmpp)(OH)(H2O)]- and 1:2 [VO 2(maltol)2]- vanadium(V) species. By using known HSA binders, competition NMR experiments revealed that both complexes preferentially bind to drug site I. Docking simulations carried out with HADDOCK together with restraints derived from the STD results led to three-dimensional models that are in agreement with the NMR spectroscopic data, providing useful information on molecular interaction modes. These results indicate that the combination of STD NMR and data-driven docking is a good tool for elucidating the interactions in protein-vanadium compounds and thus for clarifying the mechanism of drug delivery as vanadium compounds have shown potential therapeutic properties. 1H STD NMR analysis complemented by HADDOCK studies have revealed that the [VO2(dmpp)(H2O)(OH)] - species, resulting from the oxidation of the potential insulin mimetic VO(dmpp)2, binds preferentially to HSA site I. These findings corroborate the involvement of this serum protein in the transport of vanadium species in the blood stream and their delivery to target cells.
KW - Docking studies
KW - Drug delivery
KW - NMR spectroscopy
KW - Proteins
KW - Vanadium
UR - http://www.scopus.com/inward/record.url?scp=84883525535&partnerID=8YFLogxK
U2 - 10.1002/ejic.201300419
DO - 10.1002/ejic.201300419
M3 - Article
AN - SCOPUS:84883525535
SN - 1434-1948
VL - 2013
SP - 4619
EP - 4627
JO - European Journal of Inorganic Chemistry
JF - European Journal of Inorganic Chemistry
IS - 26
ER -