Request for a 500 MHz NMR console and nitrogen-cooled cryoprobe

请求 500 MHz NMR 控制台和氮冷冷冻探头

• 批准号: 10440662
• 负责人: Andrew L Lee
• 金额: $ 59.91万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10440662
• 关键词: Age; Aging; Automation; Biological; Biology; Chemicals; Communities; Data Collection; Disease; Drug Delivery Systems; Equipment; Event; Failure; Infrastructure; Libraries; Liquid substance; Location; Modernization; NMR Spectroscopy; Nitrogen; North Carolina; Pharmacy Schools; Research; Research Personnel; Sampling; Schools; Scientist; Testing; United States National Institutes of Health; Universities; Vendor; Walking; Work; design; drug discovery; experience; instrument; molecular imaging; small molecule; structural genomics

Abstract This proposal is a request to upgrade the 500 MHz NMR spectrometer that operates in the Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill (UNC Eshelman School of Pharmacy). This facility serves a community of NIH-supported medicinal chemists, chemical biologists, drug delivery scientists, and a molecular imaging methodologist with biological applications. The requested equipment is for a Bruker Neo 500 console with liquid nitrogen cooled cryoprobe and automatic sample changer. The requested upgrade equipment is critical because all of the NMR instruments in the facility are aging Varian spectrometers that have never been upgraded and are no longer supported by the vendor. None of the instruments currently have cryoprobes, and hence the sensitivity is limited, especially for the many routine 13C acquisitions that are needed for small molecule NMR. The work in the School of Pharmacy’s NMR Facility is highlighted by the existence of two centers, the Center for Integrative Chemical Biology and Drug Discovery (CICBDD, led by Dr. Stephen Frye) and the UNC footprint of the Structural Genomics Consortium (SGC-UNC, led by Dr. Tim Willson). These centers produce very large numbers of small molecules that are used in libraries or are tested for activities against a variety of disease-related targets. The syntheses of these molecules require extensive NMR characterization, and there is a large need for high-sensitivity, automated data collection to support this work, as well as the research of the other researchers included in this application. The facility is managed by an experienced manager/director team and further supported by an oversight committee and School administration. There are two locations for the spectrometers in a single building (Marsico Hall, completed in 2014), with the spaces designed specifically for NMR. This is a first-rate facility with excellent infrastructure; however, the age of the spectrometers poses a serious threat of lengthy downtime that may be very challenging to deal with in the event of hardware failure. Furthermore, convenient walk-up access to spectrometers that serve the needs of the users is becoming problematic because of limited automation and low sensitivity of existing probes. This requested equipment is the first step towards modernizing the facility through upgrades that will introduce a highly user-desirable instrument that can be relied upon for the next decade and beyond.

抽象的 该提案是对 Eshelman 学校运行的 500 MHz NMR 波谱仪进行升级的请求 北卡罗来纳大学教堂山分校（北卡罗来纳大学埃谢尔曼药学院）药学系。 该设施服务于 NIH 支持的药物化学家、化学生物学家、药物输送科学家、 以及具有生物学应用的分子成像方法学家 所需的设备适用于布鲁克。 Neo 500 控制台配备液氮冷却冷冻探头和自动进样器。 设备至关重要，因为该设施中的所有 NMR 仪器都是老化的瓦里安光谱仪， 从未升级且不再受供应商支持。目前所有仪器均未升级。 冷冻探针，因此灵敏度受到限制，特别是对于许多常规 13C 采集而言 小分子 NMR 所需的工作由药学院 NMR 设施强调。 存在两个中心，即综合化学生物学和药物发现中心（CICBDD），由 Dr. Stephen Frye）和结构基因组学联盟（SGC-UNC，由 Tim 博士领导）在 UNC 的足迹 Willson）。这些中心生产大量小分子，用于图书馆或进行测试。 用于对抗多种疾病相关靶点的活性这些分子的合成需要大量的工作。 NMR 表征，并且非常需要高灵敏度、自动化数据收集来支持这一点 工作以及本应用程序中其他研究人员的研究由该设施管理。 经验丰富的经理/总监团队，并得到监督委员会和学校的进一步支持 一座大楼（Marsico Hall，于 2017 年竣工）内设有两个光谱仪位置。 2014），拥有专门为 NMR 设计的空间，这是一个一流的设施，拥有优良的基础设施； 然而，光谱仪的老化带来了长时间停机的严重威胁，这可能会非常严重。 此外，在发生硬件故障时处理起来也很困难。 由于自动化程度和技术水平有限，满足用户需求的光谱仪正变得越来越成问题。 现有探头的低灵敏度要求设备是实现设施现代化的第一步。 通过升级，将引入用户非常想要的仪器，可以在下一步中依赖 十年及以后。

项目成果

A Unified Strategy to Improve Lipid Nanoparticle Mediated mRNA Delivery Using Adenosine Triphosphate.

使用三磷酸腺苷改善脂质纳米颗粒介导的 mRNA 递送的统一策略。

• 发表时间: 2023-09-13
• 影响因子: 15
• 作者: Ma, Yutian;Fenton, Owen S
• 通讯作者: Fenton, Owen S