Circular Dichroism Spectropolarimeter

圆二色性分光偏振计

基本信息

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
项目类别：
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

项目摘要

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的13名教职员工（包括七名由NIH支持的主要用户），CSU San Francisco，CSU San Jose和Duke University要求资金购买新的循环二科主义（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，并且不再得到供应商的支持。请求的JASCO J-815 CD包括一个自动滴定器，停止流量的附件和用于磁性CD（MCD）研究的磁铁，对许多项目教师具有巨大价值的能力。它不仅允许下面讨论的研究继续进行，而且还可以通过提供市场上最好的最新性能规范来增强我们的生物医学研究能力。它将自动化变性滴定研究，提高研究速度，提高MCD数据的敏感性，并进行时间分辨的结构研究。当前无法使用的调查途径对于正在进行的项目至关重要。长期以来，CD在UCSC的研究中发挥了关键作用。对七个主要使用者的研究可以分为四个领域：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）确定生物学上重要系统中的基本机制。区域1中的两个主要和一个次要用户将使用分光光度计来确定蛋白质和DNA结构和稳定性，并表征肽的结构和功能以进行HIV疫苗的发育。在区域2中，一名主要和一名次要用户将使用CD来表征蛋白质结构和稳定性，并在数十毫秒内监测蛋白质折叠动力学的时间更长。一个主要第3区中的一个次要用户将采用CD来获取手学数据，以阐明对疾病有效的生物活性海洋衍生的天然产物，并开发手性结构探针来研究生物底物的对映体认识。 CD将在4区的三个主要和两个次要使用者中使用，以表征生物化学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转移，细胞周期，细胞周期，昼夜节律）。一位次要用户将使用CD研究参与一氧化氮合酶催化的中间体的反应（区域4），以及单体和二聚体组蛋白（区域1）的结构和稳定性。生物医学研究是UCSC的优先事项，该研究继续扩大其教师和研究设施。 2006年完成的物理科学大楼为该部提供了79,800 ASF的空间。化学，生物化学和环境毒理学以及2012年开设了生物医学大楼。这项新的基础设施将有助于未来十年的生物医学研究大幅增长。我们由NIH资助的教师使用UCSC当前的CD来促进迫切需要生物医学需求的研究领域。但是，我们必须取代我们的老化工具，因此拟议的CD仪器对于研究人员的持续发展至关重要。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.