Microscale LC-MS and NMR Methodology for Rapid Natural *

Rapid Natural 的微型 LC-MS 和 NMR 方法 *

基本信息

  • 批准号:
    7125188
  • 负责人:
  • 金额:
    $ 37.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-09-23 至 2008-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Drug discovery from natural products can be prohibitively expensive and inefficient due to the labor and materials required for preparative-scale isolation of an active component, often before its novelty and potency can be determined. We propose to apply 10-fold more sensitive methods of mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis early in the isolation of a bioactive natural product. The novel MS interface provides a high sensitivity and resolution previously attainable only with nanobore LC-MS, with the use of larger LC columns, which allow enough material to be collected for NMR analysis. The micro-NMR method can acquire NMR spectra of all collected fractions under full automation, with a limit of quantitation below 1 mu/g, and recover the samples for bioassay. Together, these methods enable identification and quantitation of an active species concurrent with its initial isolation, eliminating the lengthy and expensive large-scale purification needed by traditional methods. The proposed methodology will be demonstrated and developed in the isolation of 3 recently-discovered protease inhibitor activities in extracts of cyanobacteria, a slow-growing, low-yield organism that has not been practical to study by traditional methods. The higher sensitivity and non-destructive nature of the new analytical methods enables enough material for analysis and bioassay to be obtained from 100-fold smaller growths, or for 100 times more strains to be grown with the same resources. The ability to perform extraction and purification on an analytical scale rather than preparative scale reduces the time required from weeks to days. These dramatic improvements have the potential to reinvigorate the field of natural products discovery. The specific aims are: 1) To implement more-sensitive, higher-recovery LC-MS methods using the recently-developed nano-splitter device. 2) To implement high-throughput NMR of fractions collected from LC-MS analysis, combining use of microcoil probes with a method for lossless loading of small volumes (2 uL) from 96-well plates. 3) To provide bioguided fractionation of cyanobacterial extracts, which are optimized for high-throughput micro-NMR and LC-MS analysis. The objective of this proposal is to improve on natural product discovery. This has the potential to directly impact on public health, by overcoming current limitations of traditional methods and reinvigorate the important field of drug discovery from natural sources.
描述(由申请人提供):由于天然产物的药物发现可能是昂贵且效率低下的,这是由于准备级别的活性成分所需的劳动和材料,通常是在确定其新颖性和效力之前。我们建议在生物活性天然产物的早期分离质谱法(MS)和核磁共振(NMR)分析的10倍更敏感的方法。新颖的MS界面可在使用较大的LC柱的情况下仅使用纳米虫LC-MS实现的高灵敏度和分辨率,从而可以收集足够的材料进行NMR分析。 Micro-NMR方法可以在完全自动化下获取所有收集分数的NMR光谱,定量限至1 mu/g,并恢复生物测定的样品。这些方法一起,可以识别和定量活性物种与最初隔离的同时进行的,从而消除了传统方法所需的冗长且昂贵的大规模纯化。该方法将在分离出3种最近发现的蛋白酶抑制剂活性中的蓝细菌提取物中进行证明和开发,蓝细菌的提取物是一种缓慢增长的低收益生物体,是通过传统方法进行研究的。新的分析方法的较高灵敏度和无损性具有足够的材料来进行分析和生物测定,从100倍较小的生长中获得,或者以相同的资源而生长100倍的菌株。在分析量表上进行提取和纯化而不是制备量表的能力减少了几周到几天所需的时间。这些戏剧性的改进有可能重振天然产品发现领域。具体目的是:1)使用最近开发的纳米切片设备实现更敏感的更高恢复LC-MS方法。 2)实施从LC-MS分析中收集的分数的高通量NMR,将Microcoil探针的使用与96孔板的无损载荷(2 ul)的方法相结合。 3)提供蓝细菌提取物的生物分级分级,可用于高通量微型NMR和LC-MS分析。该建议的目的是改善自然产品发现。通过克服当前的传统方法的局限性并振兴自然来源的药物发现领域,这有可能直接影响公共卫生。

项目成果

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JIMMY ORJALA其他文献

JIMMY ORJALA的其他文献

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{{ truncateString('JIMMY ORJALA', 18)}}的其他基金

Research Training in Natural Product Complementary and Integrative Health
天然产品补充和综合健康研究培训
  • 批准号:
    10066308
  • 财政年份:
    2013
  • 资助金额:
    $ 37.13万
  • 项目类别:
Research Training in Natural Product Complementary and Integrative Health
天然产品补充和综合健康研究培训
  • 批准号:
    10543771
  • 财政年份:
    2013
  • 资助金额:
    $ 37.13万
  • 项目类别:
Research Training in Natural Product Complementary and Integrative Health
天然产品补充和综合健康研究培训
  • 批准号:
    10320738
  • 财政年份:
    2013
  • 资助金额:
    $ 37.13万
  • 项目类别:
Cultured Cyanobacteria, Isolation Chemistry, Structure Elucudation, and Plant Acq
培养蓝藻、分离化学、结构解析和植物采集
  • 批准号:
    7302062
  • 财政年份:
    2007
  • 资助金额:
    $ 37.13万
  • 项目类别:
Project 2: Aquatic Cyanobacteria Plant Collections
项目2:水生蓝藻植物收藏
  • 批准号:
    10621871
  • 财政年份:
    2007
  • 资助金额:
    $ 37.13万
  • 项目类别:
Project 2: Aquatic Cyanobacteria Plant Collections
项目2:水生蓝藻植物收藏
  • 批准号:
    10165646
  • 财政年份:
    2007
  • 资助金额:
    $ 37.13万
  • 项目类别:
Project 2: Aquatic Cyanobacteria Plant Collections
项目2:水生蓝藻植物收藏
  • 批准号:
    10410425
  • 财政年份:
    2007
  • 资助金额:
    $ 37.13万
  • 项目类别:
Microscale LC-MS and NMR Methodology:Rapid Natural (RMI)
微型 LC-MS 和 NMR 方法:Rapid Natural (RMI)
  • 批准号:
    7011315
  • 财政年份:
    2005
  • 资助金额:
    $ 37.13万
  • 项目类别:
Microscale LC-MS and NMR Methodology:Rapid Natural (RMI)
微型 LC-MS 和 NMR 方法:Rapid Natural (RMI)
  • 批准号:
    7270499
  • 财政年份:
    2005
  • 资助金额:
    $ 37.13万
  • 项目类别:
Cultured Cyanobacteria, Isolation Chemistry, Structure Elucudation, and Plant Acq
培养蓝藻、分离化学、结构解析和植物采集
  • 批准号:
    7921382
  • 财政年份:
  • 资助金额:
    $ 37.13万
  • 项目类别:

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南卡罗来纳州临床/转化研究中心
  • 批准号:
    7216048
  • 财政年份:
    2006
  • 资助金额:
    $ 37.13万
  • 项目类别:
Quantitative Chemical Biology
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  • 批准号:
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  • 批准号:
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    $ 37.13万
  • 项目类别:
Quantitative Chemical Biology
定量化学生物学
  • 批准号:
    7121935
  • 财政年份:
    2004
  • 资助金额:
    $ 37.13万
  • 项目类别:
Multidisciplinary Clinical Research Careers Program(RMI)
多学科临床研究职业计划(RMI)
  • 批准号:
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  • 财政年份:
    2004
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  • 项目类别:
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