Improvement of the mitochondria-targeted mass spectrometry probe MitoB and development of the lipophilic triphenhylphosphonium cation as a mitochondrial delivery vector

活性氧（ROS）在病理性氧化损伤和氧化还原信号传导中起决定性作用。活性氧的生成、降解和对生物分子的反应速率对这些物种的体内分析技术至关重要。使用普通探针可以反映与抗氧化剂的竞争，而不是自由基的生成速率。这是迄今为止开发的方法无法实现的主要原因。然而，线粒体靶向质谱探针MitoB在该领域具有特殊的地位。它允许准确和有效地跟踪线粒体过氧化氢的稳态水平，过氧化氢是病理学中的一个重要参数，迄今仍在讨论中。在这个项目中，我们将研究一些改进，使MitoB成为一个更好的探针。这些包括分析技术的改进、尿液分析的建立和方法的验证。此外，还将进一步开发利用三苯膦（TPP）阳离子的线粒体靶向特性，例如使用TPP基团作为载体将小生物活性分子传递到线粒体。

Reactive oxygen species (ROS) are decisive for pathological oxidative damage and redox signalling. The reaction rates of ROS generation, degradation, and reaction against biological molecules are crucial to an in vivo analytical technique of these species. The use of common probes can reflect the competition with antioxidants, rather than the free radical generation rate. This is the major cause of inability of the developed approaches so far. However, the mitochondria-targeted mass spectrometry probe MitoB has specialty particular place in this field. It allows to accurately and efficiently follow the steady-state level of mitochondrial hydrogen peroxide, which is an important parameter in pathologies and is to date still under discussion. In this project some improvements will be investigated to make MitoB a better probe. These include improvement of the analytical technique, establishment of urine analysis, and method validation. Also, the use of the mitochondria-targeted feature of triphenhylphosphonium (TPP) cation will be further developed such as using the TPP group as a vector to deliver small bioactive molecules to the mitochondria.