Metal Coordination and DNA Interactions Control Sulfur and Selenium Antioxidant Mechanisms

金属配位和 DNA 相互作用控制硫和硒的抗氧化机制

• 批准号: 1807709
• 负责人: Julia Brumaghim
• 金额: $ 42万
• 依托单位: Clemson University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807709&HistoricalAwards=false
• 关键词: Metal; Coordination; DNA; Interactions; Control

Iron and copper ions naturally present in living systems can generate radicals that damage DNA. The control of this damage is vital. Thione and selone antioxidants, which contain sulfur and selenium, respectively, prevent DNA damage by binding iron and copper ions. Very little is known about the specific ways in which the binding of the thiones and selones to the metal ions results in antioxidant activity or how these antioxidants or their metal complexes interact with DNA to prevent radical damage. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Julia Brumaghim from Clemson University to investigate how sulfur and selenium antioxidants prevent DNA damage. The proposed investigations advance the understanding of cellular radical damage and its prevention. The investigations also represent opportunities for interdisciplinary graduate and undergraduate student training. Dr. Brumaghim contributes to the education of middle and high school teachers and students by designing an inquiry-driven lab experiment about prevention of DNA damage using tea antioxidants.Dr. Brumaghim's research focuses on a unique class of sulfur and selenium antioxidants whose biological effects are vital but poorly understood, namely thiones and selones. The study of the redox behavior of these molecules and of their biologically-relevant metal complexes leads to information that may be applicable to a wide variety of bioactive molecules that contain the same functional groups. In contrast to widely studied sulfur- and seleno-amino acids that prevent only copper-mediated DNA damage, thione and selone antioxidants prevent more DNA damage from iron than from copper. This research examines the coordination chemistry of the two antioxidants with Fe(II) and Cu(I) in an effort to elucidate the differences between their activity and that of sulfur- and selenium- containing amino acids. The research produces also information on the molecular mechanism underlying the ability of thiones and selenones to prevent DNA damage.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

自然存在于生命系统中的铁和铜离子可以产生破坏DNA的自由基。控制这种损害至关重要。 硫酮和硒酮抗氧化剂分别含有硫和硒，通过结合铁和铜离子来防止DNA损伤。 关于硫酮和硒酮与金属离子的结合导致抗氧化活性的具体方式，或者这些抗氧化剂或其金属络合物如何与DNA相互作用以防止自由基损伤，人们知之甚少。 有了这个奖项，化学部的生命过程化学计划正在资助克莱姆森大学的朱莉娅·布鲁马希姆博士研究硫和硒抗氧化剂如何防止DNA损伤。 拟议的调查推进细胞自由基损伤及其预防的理解。这些调查也代表了跨学科研究生和本科生培训的机会。 Brumaghim博士通过设计一个关于使用茶抗氧化剂预防DNA损伤的调查驱动的实验室实验，为初中和高中教师和学生的教育做出了贡献。Brumaghim博士的研究重点是一类独特的硫和硒抗氧化剂，其生物学作用至关重要但知之甚少，即硫酮和硒酮。 对这些分子及其生物学相关金属络合物的氧化还原行为的研究导致了可能适用于含有相同官能团的各种生物活性分子的信息。与广泛研究的硫氨基酸和硒氨基酸仅能防止铜介导的DNA损伤相反，铁和硒酮抗氧化剂防止铁引起的DNA损伤比铜引起的更多。本研究考察了这两种抗氧化剂与Fe（II）和Cu（I）的配位化学，以阐明它们的活性与含硫和含硒氨基酸的活性之间的差异。该研究还提供了硫酮和硒酮防止DNA损伤的分子机制的信息。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Coordination complexes of methimazole with copper: Controlling redox reactions and sulfur extrusion

• DOI: 10.1016/j.ica.2020.119568
• 发表时间: 2020-07
• 期刊: Inorganica Chimica Acta
• 影响因子: 2.8
• 作者: Jaime M. Murphy;A. Gaertner;Amanda M. Owen;Samantha Struder;C. McMillen;M. Wetzler;Julia L. Brumaghim

Zinc(II) thione and selone complexes: The effect of metal redox activity on ligand-based oxidation

• DOI: 10.1016/j.ica.2019.119379
• 发表时间: 2020-03
• 期刊: Inorganica Chimica Acta
• 影响因子: 2.8
• 作者: Bradley S. Stadelman;Jaime M. Murphy;Amanda M. Owen;Rodrigo Castro-Ramírez;Haydan C. Smith;Caleb Cohen;Lynn X. Zhang;C. A. Bayse;C. McMillen;N. Barba-Behrens;Julia L. Brumaghim

Cobalt-mediated oxidative DNA damage and its prevention by polyphenol antioxidants

• DOI: 10.1016/j.jinorgbio.2022.112024
• 发表时间: 2022-10-19
• 期刊: JOURNAL OF INORGANIC BIOCHEMISTRY
• 影响因子: 3.9
• 作者: Angele-Martinez，Carlos;Murray，Joseph;Brumaghim，Julia L.
• 通讯作者: Brumaghim，Julia L.