Research Initiation Award: Microwave Synthesis of Imidazole Compounds to Investigate Allosteric Binding to VCP

研究启动奖:微波合成咪唑化合物以研究 VCP 的变构结合

基本信息

  • 批准号:
    2000028
  • 负责人:
  • 金额:
    $ 29.55万
  • 依托单位:
  • 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:
    2020-05-01 至 2023-10-31
  • 项目状态:
    已结题

项目摘要

Research Initiation Awards provide support for junior and mid-career faculty at Historically Black Colleges and Universities who are building new research programs or redirecting and rebuilding existing research programs. It is expected that the award will (1) further the faculty member's research capability and effectiveness, (2) improve research and teaching at the home institution, and (3) engage more undergraduate students from underrepresented groups in research experiences. The project from Bowie State University, a Historically Black College/University (HBCU), seeks to study the structural requirements for allosteric binders to certain enzymatic proteins that maintain protein homeostasis in mammalian, yeast, and plant cells. The project integrates computational chemistry and biology with analogous bench research. In addition, it is designed to include undergraduate and high school students as active researchers. Collaboration and mentorship will take place throughout the project. The PI will collaborate with another researcher at Georgetown University, while the undergraduates will serve as mentors to the high school students under the supervision of the PI. VCP is an ATPase which plays a major role in the ubiquitin proteasome system (UPS). The UPS is responsible for degrading unfolded proteins through the proteasome in order to relieve cellular stress. Once tagged with ubiquitin, VCP translocates the proteins from the ER to the cytosol. VCP binders have been shown to cause an accumulation of ubiquitinated proteins which ultimately leads to cell death. This is favorable when the system is being exploited to avoid apoptosis. Six-membered ring heterocycles have been shown to act as ATP-competitive binders and are therefore unselective. Five-membered ring heterocycles bind to an allosteric site of VCP and are highly selective. However, it is unclear what the structural requirements for allosteric binders are. We propose the synthesis of imidazole compounds through a microwave-assisted multicomponent reaction in order to access a variety of imidazole compounds with numerous substitution patterns. These compounds will be tested and ultimately help define the structural requirements for allosteric binding to VCP. We will also measure the effect of these imidazoles on VCP activity and cell death.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.
研究启动奖为历史上黑人学院和大学的初级和中级职业教师提供支持,他们正在建立新的研究项目或重新定向和重建现有的研究项目。预计该奖项将(1)进一步教师的研究能力和有效性,(2)提高研究和教学在家庭机构,和(3)从事更多的本科生从研究经验的代表性不足的群体。Bowie州立大学是一所历史上的黑人学院/大学(HBCU),该项目旨在研究某些酶蛋白的变构结合剂的结构要求,这些酶蛋白在哺乳动物、酵母和植物细胞中维持蛋白质稳态。 该项目将计算化学和生物学与类似的实验室研究相结合。 此外,它的目的是包括本科生和高中学生作为积极的研究人员。合作和指导将在整个项目中进行。PI将与乔治敦大学的另一位研究人员合作,而本科生将在PI的监督下担任高中生的导师。 VCP是在泛素蛋白酶体系统(UPS)中起主要作用的ATP酶。 UPS负责通过蛋白酶体降解未折叠的蛋白质,以缓解细胞应激。一旦被泛素标记,VCP将蛋白质从ER易位到胞质溶胶。已经显示VCP结合剂引起泛素化蛋白的积累,其最终导致细胞死亡。当系统被利用以避免细胞凋亡时,这是有利的。六元环杂环已被证明是ATP竞争性结合剂,因此是非选择性的。 五元环杂环与VCP的变构位点结合,并且具有高度选择性。然而,目前还不清楚变构结合剂的结构要求是什么。我们提出通过微波辅助多组分反应合成咪唑化合物,以获得具有多种取代模式的各种咪唑化合物。 这些化合物将进行测试,并最终帮助确定变构结合VCP的结构要求。 我们还将测量这些咪唑类化合物对VCP活性和细胞死亡的影响。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

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Jacqueline Smith其他文献

Dance Composition: A Practical Guide for Teachers
舞蹈创作:教师实用指南
  • DOI:
  • 发表时间:
    1978
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Jacqueline Smith
  • 通讯作者:
    Jacqueline Smith
The Aspergillus nidulans cnxABC Locus Is a Single Gene Encoding Two Catalytic Domains Required for Synthesis of Precursor Z, an Intermediate in Molybdenum Cofactor Biosynthesis*
构巢曲霉 cnxABC 基因座是一个单基因,编码合成前体 Z(钼辅因子生物合成的中间体)所需的两个催化结构域*
  • DOI:
  • 发表时间:
    1997
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    S. Unkles;Jacqueline Smith;G. Kanan;L. Millar;I. Heck;D. Boxer;J. R. Kinghorn
  • 通讯作者:
    J. R. Kinghorn
Integration of the genetic and physical maps of the chicken macrochromosomes.
鸡大染色体遗传图谱和物理图谱的整合。
  • DOI:
    10.1046/j.1365-2052.2000.00549.x
  • 发表时间:
    2000
  • 期刊:
  • 影响因子:
    2.4
  • 作者:
    Jacqueline Smith;I. Paton;C. Bruley;D. Windsor;D. Burt;F. A. P. León;D. Burke
  • 通讯作者:
    D. Burke
Neonatal electronic resuscitation app documentation (NeRD): Electronic documentation compared to written documentation
新生儿电子复苏应用程序文档 (NeRD):电子文档与书面文档的比较
  • DOI:
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Jacqueline Smith;Asher Jakobsson;Victoria J Kain;Y. Kandasamy;Rosie Bragg
  • 通讯作者:
    Rosie Bragg
Whole genome sequencing of three native chicken varieties (Common Deshi, Hilly and Naked Neck) of Bangladesh
孟加拉国三个本土鸡品种(普通德西鸡、丘陵鸡和裸颈鸡)的全基因组测序
  • DOI:
    10.1038/s41597-024-04291-z
  • 发表时间:
    2024-12-24
  • 期刊:
  • 影响因子:
    6.900
  • 作者:
    Md Ataul Goni Rabbani;Adriana Vallejo-Trujillo;Zhou Wu;Katarzyna Miedzinska;Shakila Faruque;Kellie A. Watson;Jacqueline Smith
  • 通讯作者:
    Jacqueline Smith

Jacqueline Smith的其他文献

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{{ truncateString('Jacqueline Smith', 18)}}的其他基金

CAREER: Modulating cell signaling and migration by targeted small-molecule binding to a key regulator of protein degradation
职业:通过与蛋白质降解的关键调节因子结合的靶向小分子来调节细胞信号传导和迁移
  • 批准号:
    2239475
  • 财政年份:
    2023
  • 资助金额:
    $ 29.55万
  • 项目类别:
    Continuing Grant
Excellence in Research: Development of a Fluorescent Assay to Measure LAT1 Transport
卓越的研究:开发测量 LAT1 转运的荧光测定法
  • 批准号:
    2301301
  • 财政年份:
    2023
  • 资助金额:
    $ 29.55万
  • 项目类别:
    Standard Grant
Understanding the resilience of wild birds to climate change: seasonal genomics of the annual migratory breeding cycle
了解野生鸟类对气候变化的适应能力:年度迁徙繁殖周期的季节性基因组学
  • 批准号:
    BB/V001647/1
  • 财政年份:
    2021
  • 资助金额:
    $ 29.55万
  • 项目类别:
    Research Grant
Research Initiation Award: Novel Imidazole Compounds to Investigate the Unfolded Protein Response (UPR)
研究启动奖:用于研究未折叠蛋白反应 (UPR) 的新型咪唑化合物
  • 批准号:
    1800165
  • 财政年份:
    2018
  • 资助金额:
    $ 29.55万
  • 项目类别:
    Standard Grant
Faculty Development for Technician Education in Welding, Materials Joining, and Non-Destructive Testing
焊接、材料连接和无损检测技术人员教育师资队伍建设
  • 批准号:
    1400530
  • 财政年份:
    2014
  • 资助金额:
    $ 29.55万
  • 项目类别:
    Standard Grant
Identification of the molecular basis of differential host responses to rapidly evolving Avian Influenza viruses in different avian species
鉴定不同鸟类物种对快速进化的禽流感病毒的不同宿主反应的分子基础
  • 批准号:
    BB/L004666/1
  • 财政年份:
    2014
  • 资助金额:
    $ 29.55万
  • 项目类别:
    Research Grant
Computer Science, Engineering, Mathematic Scholarship Program
计算机科学、工程、数学奖学金计划
  • 批准号:
    9987343
  • 财政年份:
    2000
  • 资助金额:
    $ 29.55万
  • 项目类别:
    Standard Grant

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  • 批准号:
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  • 批准号:
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