Hartinger Christian G, Keppler Bernhard K
Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria.
Electrophoresis. 2007 Oct;28(19):3436-46. doi: 10.1002/elps.200700114.
With the current demographic development and the knowledge that the probability to be diagnosed with cancer increases with age, the search for new treatment options in cancer chemotherapy is of utmost importance for the society. Capillary electrophoretic methods have been applied in the last few years for studying the properties of metal-based drugs and drug candidates. Especially, the elucidation of the mode of action of such compounds could contribute significantly to design new drugs for overcoming the threat of cancer. This review article highlights the developments in metallodrug research applying CE during the last 4 years and follows a review from 2003 (Hartinger, C. G., Timerbaev, A. R., Keppler, B. K., Electrophoresis 2003, 24, 2023-2037). Most importantly the broadening of application areas of CE must be noted: especially the binding studies of metal complexes toward proteins (including the determination of association and rate constants), following redox reactions of metal complexes and their influence on the reactivity toward biotargets, etc. are important development areas of the last few years. In parallel with these new applications goes the usage of new or modified separation methods including microemulsion EKC or ACE, or the advantageous use of equipping the CE system with mass spectrometric detectors such as inductively coupled plasma (ICP) or ESI mass spectrometers (MS) for determining the degree of metallation of a protein or characterizing the adducts. Finally, upcoming requirements for expanding the method's application area are discussed including studies on new targets in the cell, analyzing real-world samples, methodological development, and contributions to improve the design of new anticancer agents.
随着当前人口结构的发展以及人们认识到患癌概率会随着年龄增长而增加，寻找癌症化疗的新治疗方案对社会而言至关重要。在过去几年中，毛细管电泳方法已被应用于研究金属基药物及候选药物的性质。尤其是，阐明此类化合物的作用方式对于设计克服癌症威胁的新药可能会有显著贡献。这篇综述文章重点介绍了过去4年中应用毛细管电泳进行金属药物研究的进展，并延续了2003年的一篇综述（Hartinger, C. G., Timerbaev, A. R., Keppler, B. K., Electrophoresis 2003, 24, 2023 - 2037）。最重要的是必须注意到毛细管电泳应用领域的拓宽：特别是金属配合物与蛋白质的结合研究（包括缔合常数和速率常数的测定）、金属配合物的氧化还原反应及其对与生物靶点反应活性的影响等，都是过去几年重要的发展领域。与这些新应用并行的是新的或改进的分离方法的使用，包括微乳液电动色谱或亲和毛细管电泳，或者有利地使用配备电感耦合等离子体质谱（ICP）或电喷雾电离质谱（ESI MS）等质谱检测器的毛细管电泳系统来测定蛋白质的金属化程度或表征加合物。最后，讨论了扩大该方法应用领域的未来需求，包括对细胞中新靶点的研究、分析实际样品、方法学开发以及对改进新型抗癌药物设计的贡献。
