High-Throughput Solid-Phase Combinatorial Biocatalysis

高通量固相组合生物催化

基本信息

  • 批准号:
    6849747
  • 负责人:
  • 金额:
    $ 68.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-02-03 至 2008-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Rapid developments in genomics, proteomics, and combinatorial chemistry have reshaped the field of drug discovery, providing new drug targets for selective screens and new compounds to be tested in those screens. While combinatorial methods have given rise to large libraries of compounds, typically these compounds result in improved lead candidates that must undergo further transformations by conventional medicinal chemistry to yield new drug candidates. Bioengineering, in the context of high-throughput combinatorial methodologies, has not impacted lead optimization nearly as much as it has lead discovery, mainly because of the highly selective, intricate chemistries often required to optimize lead compounds and the lack of a suitably broad high-throughput platform. Combinatorial biocatalysis can help overcome these obstacles by exploiting the exquisite selectivity and unique reactivity of enzymes and microbial biocatalysts; however, to date this technology has been limited to the derivatization of soluble substrates. We propose to expand the scope of combinatorial biocatalysis to include reactions on, and the generation of libraries from, lead molecules attached to solid and soluble polymer supports. In the process, we will develop a high-throughput, biocatalytic technology for drug discovery. The specific aims are: 1. To expand the breadth of biocatalysis on solid- and polymer-supported compounds in aqueous and nonaqueous media; 2. To develop strategies for attaching lead compounds and removing their derivatives from solid and polymeric supports; 3. To demonstrate high-throughput, combinatorial biocatalytic lead optimization of complex natural and synthetic molecules, screen resulting derivatives for biological activity, and scale up structurally and functionally interesting derivatives using biotransformations. A series of lead molecules will be used in this work, ranging from enzyme substrates that are attached onto solid and soluble polymer supports to complex compounds (the flavonoid bergenin and the current HIV-1 protease inhibitor indinavir). Successful completion of this research program will result in a powerful methodology that can be used by biomedical investigators in the search for new, more potent small molecule therapeutics.
描述(由申请人提供):基因组学、蛋白质组学和组合化学的快速发展重塑了药物发现领域,为选择性筛选提供了新的药物靶点和在这些筛选中测试的新化合物。虽然组合方法已经产生了大量的化合物库,但通常这些化合物会产生改进的候选先导物,这些候选先导物必须经过传统药物化学的进一步转化才能产生新的候选药物。在高通量组合方法的背景下,生物工程对先导物优化的影响不如对先导物发现的影响大,主要是因为先导物优化通常需要高度选择性、复杂的化学反应,而且缺乏合适的广泛的高通量平台。组合生物催化可以通过利用酶和微生物催化剂的精细选择性和独特的反应性来帮助克服这些障碍;然而,到目前为止,这项技术仅限于可溶性底物的衍生化。我们建议扩大组合生物催化的范围,包括铅分子附着在固体和可溶性聚合物载体上的反应和文库的生成。在此过程中,我们将开发一种用于药物发现的高通量生物催化技术。具体目标是:

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Jonathan S. Dordick其他文献

Role, binding properties, and potential therapeutical use of glycosaminoglycans and mimetics in SARS-CoV-2 infection. In memory of Dr. Robert Linhardt (1953–2025)
糖胺聚糖及其模拟物在 SARS-CoV-2 感染中的作用、结合特性和潜在治疗用途。纪念罗伯特·林哈特博士(1953-2025 年)
  • DOI:
    10.1016/j.carbpol.2025.123703
  • 发表时间:
    2025-08-15
  • 期刊:
  • 影响因子:
    12.500
  • 作者:
    Vitor H. Pomin;Fuming Zhang;Jonathan S. Dordick
  • 通讯作者:
    Jonathan S. Dordick
Patents and literature biocatalysis in nonaqueous media
Facile pretreatment of lignocellulosic biomass at high loadings in room temperature ionic liquids
在室温离子液体中高负载量轻松预处理木质纤维素生物质
  • DOI:
    10.1002/bit.23266
  • 发表时间:
    2011-12
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    Hong Wu;Mauricio Mora-Pale;Jian-Jun Miao;Thomas V. Doherty;Robert J. Linhardt;Jonathan S. Dordick
  • 通讯作者:
    Jonathan S. Dordick
Enzyme-based formulations for decontamination: current state and perspectives
  • DOI:
    10.1007/s00253-013-4797-x
  • 发表时间:
    2013-03-10
  • 期刊:
  • 影响因子:
    4.300
  • 作者:
    Navdeep Grover;Cerasela Zoica Dinu;Ravi S. Kane;Jonathan S. Dordick
  • 通讯作者:
    Jonathan S. Dordick
Endolysin-based autolytic E. coli system for facile recovery of recombinant proteins
基于内溶素的自溶大肠杆菌系统,可轻松回收重组蛋白
  • DOI:
    10.1021/acs.jafc.1c00059
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    6.1
  • 作者:
    Jian Zha;Zhiqiang Liu;Runcong Sun;Guoli Gong;Jonathan S. Dordick;Xia Wu
  • 通讯作者:
    Xia Wu

Jonathan S. Dordick的其他文献

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{{ truncateString('Jonathan S. Dordick', 18)}}的其他基金

Remote Electromagnetic Control of Neural Activity for Treatment of Parkinson's Disease
神经活动的远程电磁控制治疗帕金森病
  • 批准号:
    9890014
  • 财政年份:
    2016
  • 资助金额:
    $ 68.98万
  • 项目类别:
High-Throughput Platform for Identifying Stem Cell Toxicity
用于识别干细胞毒性的高通量平台
  • 批准号:
    8217894
  • 财政年份:
    2011
  • 资助金额:
    $ 68.98万
  • 项目类别:
High-Throughput Platform for Identifying Stem Cell Toxicity
用于识别干细胞毒性的高通量平台
  • 批准号:
    8404019
  • 财政年份:
    2011
  • 资助金额:
    $ 68.98万
  • 项目类别:
High-Throughput Platform for Identifying Stem Cell Toxicity
用于识别干细胞毒性的高通量平台
  • 批准号:
    8573021
  • 财政年份:
    2011
  • 资助金额:
    $ 68.98万
  • 项目类别:
Development of a Bioengineered Heparin from a Non-Animal Source
开发非动物来源的生物工程肝素
  • 批准号:
    8294884
  • 财政年份:
    2009
  • 资助金额:
    $ 68.98万
  • 项目类别:
An Artificial Golgi: Controlled GAG Synthesis and Screening
人工高尔基体:受控 GAG 合成和筛选
  • 批准号:
    7945295
  • 财政年份:
    2009
  • 资助金额:
    $ 68.98万
  • 项目类别:
Development of a Bioengineered Heparin from a Non-Animal Source
开发非动物来源的生物工程肝素
  • 批准号:
    8016845
  • 财政年份:
    2009
  • 资助金额:
    $ 68.98万
  • 项目类别:
Development of a Bioengineered Heparin from a Non-Animal Source
开发非动物来源的生物工程肝素
  • 批准号:
    7699173
  • 财政年份:
    2009
  • 资助金额:
    $ 68.98万
  • 项目类别:
Development of a Bioengineered Heparin from a Non-Animal Source
开发非动物来源的生物工程肝素
  • 批准号:
    7904164
  • 财政年份:
    2009
  • 资助金额:
    $ 68.98万
  • 项目类别:
Development of a Bioengineered Heparin from a Non-Animal Source
开发非动物来源的生物工程肝素
  • 批准号:
    8463596
  • 财政年份:
    2009
  • 资助金额:
    $ 68.98万
  • 项目类别:

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墨西哥湾沿岸联盟 (GCC) 研究评估和商业化中心
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