Institute of Optical Materials and Technologies "Acad. J. Malinowski", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Faculty of Chemistry and Pharmacy, Sofia University "St. Kl. Ohridski", 1164 Sofia, Bulgaria.
J Inorg Biochem. 2021 Jan;214:111309. doi: 10.1016/j.jinorgbio.2020.111309. Epub 2020 Nov 10.
Metal cations are key players in a plethora of essential biological processes. Over the course of evolution specific biological functions have been bestowed upon two dozen of (biogenic) metal species, some of the most frequently found being sodium, potassium, magnesium, calcium, zinc, manganese, iron, and copper. On the other hand, there is a group of less studied abiogenic metals like lithium, strontium and gallium that possess not known functions in living organisms, but, by mimicking the native ions and/or competing with them for binding to key metalloenzymes, may exert beneficial effect on humans in particular medical conditions. This review summarizes and critically examines the mechanisms of gallium's therapeutic action in anticancer and antibacterial therapies by exploiting the tools of molecular modeling and experimental biochemistry. These approaches allow for identifying key factors for Ga beneficial effect such as the electrostatic interactions with the protein ligands, substrates or bacterial siderophores, intramolecular hydrogen bond formation, and pH and dielectric properties of the medium. Several intriguing questions concerning the gallium competition with the native ferric ion have found their answers.
金属阳离子是众多重要生物过程中的关键参与者。在进化过程中，二十几种（生物源）金属物种被赋予了特定的生物学功能，其中最常见的是钠、钾、镁、钙、锌、锰、铁和铜。另一方面，还有一群研究较少的非生物源金属，如锂、锶和镓，它们在生物体中没有已知的功能，但通过模拟天然离子并/或与它们竞争结合关键金属酶，可能对人类特别是在某些医学条件下产生有益的影响。本综述通过分子建模和实验生物化学的手段，总结和批判性地考察了镓在抗癌和抗菌治疗中的治疗作用机制。这些方法可以确定 Ga 有益效果的关键因素，如与蛋白质配体、底物或细菌铁载体的静电相互作用、分子内氢键形成以及介质的 pH 值和介电性质。关于镓与天然铁离子竞争的几个有趣问题已经找到了答案。
