Circular Dichroism Spectropolarimeter

圆二色性分光偏振计

• 批准号: 8639931
• 负责人: DAVID S. KLIGER
• 金额: $ 13.2万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639931
• 关键词: 20 year old; Aging; Area; Binding; Biochemical Process; Biochemistry; Biological; Biological Factors; Biomedical Research; Catalysis; Cell Cycle; Chemistry; Circadian Rhythms; Circular Dichroism; Coupled; DNA Structure; Data; Development; Disease; Electron Transport; Faculty; Funding; HIV vaccine; Histones; Investigation; Kinetics; Light; Magnetism; Maintenance; Marines; Marketing; Metals; Minor; Monitor; Neurons; Nitric Oxide Synthase; Peptides; Performance; Play; Proteins; Protons; Reaction; Research; Research Infrastructure; Research Personnel; Role; San Francisco; Science; Signal Transduction; Structure; System; Time; Titrations; United States National Institutes of Health; Universities; Vendor; circular magnetic dichroism; environmental toxicology; improved; instrument; instrumentation; member; millisecond; physical science; protein folding; protein structure; repaired; research facility; vaccine development

DESCRIPTION (provided by applicant): Thirteen faculty members (including seven NIH-supported major users) from UC Santa Cruz, and CSU San Francisco, CSU San Jose, and Duke University request funds to purchase a new circular dichroism (CD) spectrometer. Our existing departmental CD instrument is over 20 years old, frequently needs repairs, and is no longer supported by the vendor. The requested JASCO J-815 CD includes an automated titrator, a stopped-flow attachment, and a magnet for magnetic CD (MCD) studies, capabilities of great value to many of the project faculty. It will not only allow the continuation of research discussed below, but also enhance our biomedical research capability by providing the best state-of-the-art performance specifications on the market. It will automate denaturant titration studies, increasing research pace, improve sensitivity of MCD data, and make possible time-resolved structural studies. Such currently unavailable investigative paths are vital for ongoing projects. CD has long played a critical role in research at UCSC. Research of the seven major users can be divided into four areas: 1) protein/DNA structure and functional investigations, 2) protein folding kinetic mechanisms, 3) stereochemical structure elucidation, and 4) determination of fundamental mechanisms in biologically significant systems. Two major and one minor user in Area 1 will use the spectrophotometer to determine protein and DNA structure and stability and to characterize structure and function of peptides for HIV vaccine development. In Area 2, one major and one minor user will employ CD to characterize protein structure and stability and monitor protein folding kinetics at times longer than tens of milliseconds. One major and one minor user in Area 3 will employ CD to obtain chiroptical data for structural elucidation of bioactive marine-derived natural products that are potent against disease, and for development of chiral structural probes to study enantiomeric recognition of biological substrates. CD will be used by three major and two minor users in Area 4 to characterize protein structure and mechanisms in biochemical processes (light-dependent energy conversion and signal transduction, metal binding in neuron maintenance and neuronal disease, coupled electron transfer and proton translocation, cell cycle, circadian rhythm). One minor user will use CD to investigate the reaction of intermediates involved in nitric oxide synthase catalysis (Area 4), as well as the structure and stability of monomeric and dimeric histones (Area 1). Biomedical research is a priority at UCSC, which continues to expand its faculty and research facilities. A Physical Sciences Building, completed in 2006, provides 79,800 asf of space for the Depts. of Chemistry and Biochemistry and Environmental Toxicology, and a Biomedical Sciences Building was opened in 2012. This new infrastructure will facilitate a large increase in biomedical research over the next decade. Our NIH-funded faculty have used UCSC's current CD to advance research areas of pressing biomedical need. However, we must replace our aging instrumentation, so the proposed CD instrument is vital to the continued advancement of our researchers.

描述（由申请人提供）：来自加州大学圣克鲁斯分校、加州州立大学旧金山分校、科罗拉多州立大学圣何塞分校和杜克大学的 13 名教员（包括 7 名 NIH 支持的主要用户）请求资金购买新的圆二色性 (CD) 光谱仪。我们现有的部门 CD 仪器已有 20 多年的历史，经常需要维修，并且不再获得供应商的支持。所要求的 JASCO J-815 CD 包括自动滴定仪、停流附件和用于磁性 CD (MCD) 研究的磁铁，这些功能对许多项目人员来说具有巨大价值。它不仅可以继续进行下面讨论的研究，还可以通过提供市场上最先进的性能规格来增强我们的生物医学研究能力。它将实现变性剂滴定研究的自动化，加快研究速度，提高 MCD 数据的灵敏度，并使时间分辨结构研究成为可能。这种目前不可用的调查途径对于正在进行的项目至关重要。 CD 长期以来在 UCSC 的研究中发挥着关键作用。七大用户的研究可分为四个领域：1）蛋白质/DNA结构和功能研究，2）蛋白质折叠动力学机制，3）立体化学结构阐明，4）确定具有生物学意义的系统的基本机制。 1 区的两名主要用户和一名次要用户将使用分光光度计来确定蛋白质和 DNA 的结构和稳定性，并表征用于 HIV 疫苗开发的肽的结构和功能。在区域 2 中，一名主要用户和一名次要用户将使用 CD 来表征蛋白质结构和稳定性，并在超过数十毫秒的时间内监测蛋白质折叠动力学。一个专业 3 区的一个小用户将使用 CD 来获取手性光学数据，用于对具有生物活性的海洋来源的天然产物进行结构阐明，这些天然产物具有有效的抗病能力，并用于开发手性结构探针来研究生物底物的对映体识别。 CD 将被第 4 区的三个主要用户和两个次要用户用来表征生化过程中的蛋白质结构和机制（光依赖性能量转换和信号转导、神经元维持和神经元疾病中的金属结合、耦合电子转移和质子易位、细胞周期、昼夜节律）。一名小用户将使用 CD 研究一氧化氮合酶催化中涉及的中间体的反应（区域 4），以及单体和二聚组蛋白的结构和稳定性（区域 1）。生物医学研究是 UCSC 的首要任务，该校不断扩大其师资队伍和研究设施。物理科学大楼于 2006 年竣工，为各部门提供了 79,800 平方英尺的空间。化学、生物化学和环境毒理学系以及生物医学科学大楼于 2012 年启用。这一新的基础设施将促进未来十年生物医学研究的大幅增长。我们由 NIH 资助的教师使用 UCSC 现有的 CD 来推进紧迫的生物医学需求的研究领域。然而，我们必须更换老化的仪器，因此拟议的 CD 仪器对于我们研究人员的持续进步至关重要。

项目成果

Introduction of d-Glutamate at a Critical Residue of Aβ42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity.

• DOI: 10.1002/chem.201601763
• 发表时间: 2016-08-16
• 期刊: CHEMISTRY-A EUROPEAN JOURNAL
• 影响因子: 4.3
• 作者: Warner, Christopher J. A.;Dutta, Subrata;Foley, Alejandro R.;Raskatov, Jevgenij A.
• 通讯作者: Raskatov, Jevgenij A.

Suppression of Oligomer Formation and Formation of Non-Toxic Fibrils upon Addition of Mirror-Image Aβ42 to the Natural l-Enantiomer.

• DOI: 10.1002/anie.201706279
• 发表时间: 2017-09-11
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Dutta S;Foley AR;Warner CJA;Zhang X;Rolandi M;Abrams B;Raskatov JA
• 通讯作者: Raskatov JA