Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal.
Departamento de Química e Farmácia, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
Chem Asian J. 2017 Aug 17;12(16):2062-2084. doi: 10.1002/asia.201700469. Epub 2017 Jul 20.
[VO(acac) ] 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) ] 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 [V O(acac)(apoHTF)] complexes with residues of the HTF binding sites. No indication of binding of [VO(acac) ] to HSA is obtained. We conclude that V O-acac species may be transported in blood by transferrin. At very low complex concentrations speciation calculations suggest that [(VO)(apoHTF)] species form.
[VO(acac)]是一种很有特点的钒化合物，有作为治疗药物的潜力。阐明它在血液中的运输方式很重要，但关于其与血清蛋白结合的报告一直存在矛盾。我们使用几种光谱和质谱技术（ESI 和 MALDI-TOF）、小角 X 射线散射和尺寸排阻色谱（SEC）来表征含有[VO(acac)]和人血清转铁蛋白（apoHTF）或白蛋白（HSA）的溶液。进行 DFT 和建模蛋白计算以揭示与 apoHTF 的结合类型。测量的圆二色光谱、SEC 和 MALDI-TOF 数据清楚地证明，至少有两个 VO-acac 部分可以与 apoHTF 结合，很可能形成与 HTF 结合位点的残基的[V O(acac)(apoHTF)]配合物。没有得到[VO(acac)]与 HSA 结合的迹象。我们得出结论，V O-acac 物种可能通过转铁蛋白在血液中运输。在非常低的配合物浓度下，形态分析计算表明[(VO)(apoHTF)]物种形成。
