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.

摘要 该提案是对运行在埃谢曼学校的500兆赫核磁共振波谱仪进行升级的请求 北卡罗来纳大学教堂山分校(北卡罗来纳大学伊谢尔曼药学院)药学专业。这 该机构为美国国立卫生研究院支持的药物化学家、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。所要求的设备是给布鲁克的 NEO 500控制台，配有液氮冷却低温探头和自动换样器。请求的升级 设备至关重要，因为该设施中的所有核磁共振仪器都是老化的瓦里安光谱仪 从未升级过，不再受供应商支持。目前没有一种乐器有 冷冻探头，因此灵敏度是有限的，特别是对于许多常规的13C采集， 小分子核磁共振所需的。药学院核磁共振设施的工作重点是 存在两个中心，综合化学生物学和药物发现中心(CICBDD)，由Dr。 Stephen Frye)和由Tim博士领导的结构基因组联盟(SGC-UNC)的UNC足迹 威尔森)。这些中心产生大量的小分子，用于图书馆或进行测试 针对各种与疾病有关的目标的活动。这些分子的合成需要大量的 核磁共振表征，需要高灵敏度、自动化的数据收集来支持这一点 工作，以及包括在本申请中的其他研究人员的研究。该设施由 经验丰富的经理/董事团队，并得到监督委员会和学校的进一步支持 行政管理。光谱仪在一栋建筑中有两个位置(Marsico Hall，于#年完工 2014)，空间是专门为核磁共振设计的。这是一流的设施，拥有一流的基础设施； 然而，光谱仪的使用年限造成了长时间停机的严重威胁，这可能会非常 在发生硬件故障时难以处理。此外，方便的无电梯通道 满足用户需求的光谱仪正变得有问题，因为有限的自动化和 现有探头灵敏度低。所要求的设备是实现设施现代化的第一步 通过升级，这将引入一种高度用户期望的仪器，可以在下一步依赖 十年甚至更久。

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。

• DOI: 10.1021/jacs.3c05574
• 发表时间: 2023
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Ma,Yutian;Fenton,OwenS
• 通讯作者: Fenton,OwenS