Targeted Zinc Photocages for Studying Biological Signaling

用于研究生物信号传导的靶向锌光笼

• 批准号: 2004088
• 负责人: Shawn Burdette
• 金额: $ 45.17万
• 依托单位: Worcester Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2004088&HistoricalAwards=false
• 关键词: Targeted; Zinc; Photocages; Studying; Biological

With this award, the Chemistry of Life Processes Program in the Division of Chemistry is funding Dr. Shawn Burdette at Worcester Polytechnic Institute to develop chelators that undergo light-induced reactions to release zinc in cells. Metal ions play essential roles in numerous processes that sustain life. Among these important roles, metal ions carry the signals that enable learning, memory, and movement. While the function of metal ions such as sodium, potassium and calcium are well established, the role of zinc ions, save for their role in specific zinc metalloenzymes, is less well understood. Dr. Shawn Burdette of Worcester Polytechnic Institute designs and makes tools that trap zinc ions until a light source releases the metal ion at the desired time and location. This project combines elements of synthetic chemistry with spectroscopic and biological methodologies to develop new tools to study zinc in cells. Several educational activities are integrated into a plan that includes involving home-schooled students in research activities through the Worcester Think Tank. Students in the Think Tank program come from the diverse Worcester, Massachusetts community, where over 40% of the residents belong to underrepresented groups. This collaborative effort crosses traditional disciplines of science and utilizes a hands-on research experience to promote teaching chemistry through inquiry.Vesicular zinc was found in neurons decades ago, but many roles of loosely bound zinc in signal transduction remain ambiguous. Despite the lack of definitive mechanisms, circumstantial evidence suggests zinc can modulate the activity of a variety of ion channels, and zinc interactions with cell surface receptors may lead to a variety of intracellular responses. The central obstacle to studying zinc signaling is a lack of methodologies for mimicking zinc fluctuations in biological systems with spatial and temporal control. Dr. Burdette is approaching this deficiency by applying principles of metal chelator design with the photo-reactivity of xanthone and nitro-phenylacetic acid derivatives. Taking advantage of a light-induced decarboxylation reaction, zinc can be released inside cells with an appropriate light source. This project provides the tools necessary to study zinc signaling as well as establishes the methods necessary to apply those tools in a biological environment. The research objectives are combined with educational objectives that address the lack of access home schooled students have to laboratory facilities, but also exposes those students to innovative research.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.

有了这个奖项，化学系的生命过程化学项目正在资助伍斯特理工学院的Shawn Burdette博士开发螯合剂，这些螯合剂可以通过光诱导反应在细胞中释放锌。金属离子在维持生命的许多过程中发挥着重要作用。在这些重要作用中，金属离子携带使学习，记忆和运动成为可能的信号。虽然金属离子如钠、钾和钙的功能已得到充分证实，但锌离子的作用，除了它们在特定锌金属酶中的作用外，还不太清楚。伍斯特理工学院的Shawn Burdette博士设计并制造了捕获锌离子的工具，直到光源在所需的时间和位置释放金属离子。该项目将合成化学元素与光谱和生物学方法相结合，以开发新的工具来研究细胞中的锌。几项教育活动被纳入一项计划，其中包括通过伍斯特智囊团让在家上学的学生参与研究活动。智囊团计划的学生来自不同的伍斯特，马萨诸塞州社区，其中超过40%的居民属于代表性不足的群体。这种合作努力跨越了传统的科学学科，并利用实践研究经验，通过探究促进化学教学。几十年前，在神经元中发现了囊泡锌，但松散结合的锌在信号转导中的许多作用仍然不明确。尽管缺乏明确的机制，间接证据表明，锌可以调节各种离子通道的活性，锌与细胞表面受体的相互作用可能会导致各种细胞内的反应。研究锌信号传导的主要障碍是缺乏模拟具有空间和时间控制的生物系统中锌波动的方法。Burdette博士正在通过将金属螯合剂设计原理与氧杂蒽酮和硝基苯乙酸衍生物的光反应性相结合来解决这一缺陷。利用光诱导的脱羧反应，锌可以在适当的光源下释放到细胞内。该项目提供了研究锌信号传导所需的工具，并建立了在生物环境中应用这些工具所需的方法。研究目标与教育目标相结合，解决了家庭教育学生缺乏实验室设施的问题，但也使这些学生接触到创新研究。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

Improved Photodecarboxylation Properties in Zinc Photocages Constructed Using m‐ Nitrophenylacetic Acid Variants**

使用 m-硝基苯乙酸变体构建的锌光笼中的光脱羧性能得到改善**

• DOI: 10.1002/cptc.202200102
• 发表时间: 2022
• 期刊: ChemPhotoChem
• 影响因子: 3.7
• 作者: Shigemoto, Austin K.;Bhattacharjee, Avik;Hickey, Erin E.;Boyd, Hallee Jade;McCormick, Theresa M.;Burdette, Shawn C.
• 通讯作者: Burdette, Shawn C.

Time-resolved β-lactam cleavage by L1 metallo-β-lactamase.

• DOI: 10.1038/s41467-022-35029-3
• 发表时间: 2022-11-30
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Wilamowski M;Sherrell DA;Kim Y;Lavens A;Henning RW;Lazarski K;Shigemoto A;Endres M;Maltseva N;Babnigg G;Burdette SC;Srajer V;Joachimiak A
• 通讯作者: Joachimiak A

Isothermal Titration Calorimetry for Characterizing the Zinc(II)‐Binding Properties of Photocaged Complexes with Micromolar Affinity

等温滴定量热法表征具有微摩尔亲和力的光笼配合物的锌 (II) 结合特性

• DOI: 10.1002/anse.202200043
• 发表时间: 2022
• 期刊: Analysis & Sensing
• 作者: Hickey, Erin E.;Shigemoto, Austin;Gericke, Arne;Burdette, Shawn C.
• 通讯作者: Burdette, Shawn C.