Unveiling the Interaction of Vanadium Compounds with Human Serum Albumin by Usi...

• Autor(es): Dias, David M. ; Rodrigues, João P. G. L. M. ; Domingues, Neuza S. ; Bonvin, Alexandre M. J. J. ; Castro, M. M. C. A.
• Data: 2013
• Identificador Persistente: http://hdl.handle.net/10316/25715
• Origem: Estudo Geral - Universidade de Coimbra
• Assunto(s): Proteins; Docking studies; Drug delivery; Vanadium; NMR spectroscopy
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

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 [VO2(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. Financial support by the Portuguese Fundação para a Ciência e Tecnologia (FCT) within the Programa Nacional de Reequipamento Científico Varian (contract number REDE/1517/ RMN/2005) as part of the Portuguese-NMR network (Rede Nacional de RMN) is acknowledged. D. M. D. thanks the The European NMR Large Scale Facility Utrecht for the contact with SONNMRLSF (project number BIO-NMR-00041). A. M. J. J. B. and J. R. acknowledge funding from the Dutch Foundation for Scientific Research (NWO) (VICI grant number 700.56.442) and Utrecht University (Focus and Massa grant).