Interaction of [VIVO(acac)2] with Human Serum Transferrin and Albumin

5 years ago

Interaction of [VIVO(acac)2] with Human Serum Transferrin and Albumin

Teresa Santos-Silva, Fernanda Marques, Somnath Roy, Nádia Ribeiro, Gonçalo Justino, Marino F.A. Santos, Isabel Correia, José L. Capelo, Maxim L. Kuznetsov, Ielyzaveta Chorna, Hugo M. Santos, Isabel Cavaco, James Doutch, João Costa Pessoa

[VO(acac)2] is a remarkable vanadium compound and has potential as a therapeutic drug. It is important to clarify how it is transported in blood, but the reports addressing its binding to serum proteins have been contradictory. We use several spectroscopic and mass spectrometric techniques (ESI and MALDI-TOF), small-angle X-ray scattering and size exclusion chromatography (SEC) to characterize solutions containing [VO(acac)2] and either human serum apotransferrin (apoHTF) or albumin (HSA). DFT and modeling protein calculations are carried out to disclose the type of binding to apoHTF. The measured circular dichroism spectra, SEC and MALDI-TOF data clearly prove that at least two VO–acac moieties may bind to apoHTF, most probably forming [VIVO(acac)(apoHTF)] complexes with residues of the HTF binding sites. No indication of binding of [VO(acac)2] to HSA is obtained. We conclude that VIVO–acac species may be transported in blood by transferrin. At very low complex concentrations speciation calculations suggest that [(VO)(apoHTF)] species form. Synopsis: Several distinct experimental and theoretical procedures are used to characterize solutions containing [VO(acac)2] and either human serum apotransferrin (apoHTF) or albumin. The measured circular dichroism spectra and MALDI-TOF data proves that at least two VO–acac moieties may bind to apoHTF, most probably forming [VO(acac)(apoHTF)] complexes with residues of the HTF binding sites.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/asia.201700469