Chicago Tri-Institutional Center for Chemical Methods and Library Development

芝加哥三机构化学方法和图书馆开发中心

• 批准号: 8326708
• 负责人: SERGEY A KOZMIN
• 金额: $ 189.59万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326708
• 关键词: Address; Amphotericin B; Area; Award; Biological; Biological Factors; Biology; Catalysis; Cells; Chemicals; Chemistry; Chicago; Communicable Diseases; Communities; Complex; Core Facility; Development; Engineering; Equipment; Erythromycin; Exposure to; Funding; General Population; Generations; Genomics; Goals; Gold; Illinois; Immobilization; Immunology; Individual; Institutes; Institution; Internships; Laboratories; Lead; Letters; Libraries; Link; Medicine; Methods; Mission; Molecular Bank; Monitor; Nitrogen; Organic Synthesis; Palladium; Pharmaceutical Preparations; Physical condensation; Probability; Problem Solving; Process; Production; Qualifying; Reaction; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resource Development; Resources; Scientist; Screening procedure; Series; Sirolimus; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Students; Surface; Systems Biology; Therapeutic; Training; Translating; Translations; United States National Institutes of Health; Universities; Work; base; cheminformatics; cycloaddition; design; graduate student; high throughput analysis; high throughput screening; innovation; interest; lectures; meetings; miniaturize; monolayer; next generation; oncology; operation; outreach; programs; research facility; scaffold; skills; small molecule; small molecule libraries; success; undergraduate student

DESCRIPTION (provided by applicant): The main objective of our application to NIH is to establish the Chicago Tri-lnstitutional Center for Chemical Methods and Library Development (CTCMLD), which is designed to address the fundamental challenges of high-throughput organic synthesis and to provide major advances that will significantly facilitate the development of small-molecule libraries for broad biological screening. Our CTCMLD application is strongly supported by the three participating institutions and the Chicago Biomedical Consortium, which provided a $2 Million Lever Award to match the NIH funding. The CTCMLD will have several major goals listed below. Center Objective 1: Conduct four highly integrated projects that are designed to significantly facilitate the generation of chemical diversity and assembly of high-quality small-molecule libraries. The four proposed projects are: (a) practical synthesis of new nitrogen-based heterocyclic libraries (leaders: Scheldt and Gevorgyan); (b) multi-component assembly of polyketide libraries (leader: Yamamoto); (c) assembly of scaffold-unbiased small-molecule libraries (leader: Kozmin); and (d) development of tailored surfaces for new reaction development, miniaturized library synthesis and small-molecule immobilization (leader: Mrksich). The scientific projects will be carried out at the highest level, resulting in the development of an arsenal of new synthetic methods, which in turn will enable the generation of approximately 20,000 new compounds of 20 mg scale in highly efficient, parallel manner. Center Objective 2: Training the next generation of scientists, who will develop and arsenal of new methods and strategies for high-throughput organic synthesis. Center Objective 3: Establish core research facility for library synthesis, characterization and cheminformatics. The Core facility will have three highly integrated components: High-Throughput Synthesis Component located at the University of Chicago, Hit-to-Lead Development Resource located on Northwestern campus and Cheminformatics Core at the University of Illinois at Chicago. Objective 4: Provide broad outreach to the biology community enabling rapid and efficient screening of new compound libraries. In addition to providing new compounds for the NIH Roadmap Molecular Libraries Initiative, we will collaborate with three major high-throughput screening centers in Illinois, and many individual biology laboratories. The increased connectivity and synergy resulting from the work of the CTCMLD will represent a major advance in the Chicago area's capabilities and a paradigm shift in how the Chicago academic community will approach and solve problems at the interface of chemistry, biology and medicine.

描述（由申请人提供）：我们向 NIH 申请的主要目标是建立芝加哥化学方法和库开发三机构中心 (CTCMLD)，该中心旨在解决高通量有机合成的基本挑战，并提供重大进展，从而显着促进用于广泛生物筛选的小分子库的开发。我们的 CTCMLD 申请得到了三个参与机构和芝加哥生物医学联盟的大力支持，该联盟提供了 200 万美元的杠杆奖来匹配 NIH 的资金。 CTCMLD 将有以下几个主要目标。中心目标 1：开展四个高度集成的项目，旨在显着促进化学多样性的生成和高质量小分子库的组装。拟议的四个项目是： (a) 新型氮基杂环库的实际合成（领导者：Schaldt 和 Gevorgyan）； (b) 聚酮化合物库的多组分组装（领导者：Yamamoto）； (c) 支架无偏小分子文库的组装（领导者：Kozmin）； (d) 开发用于新反应开发、小型化库合成和小分子固定的定制表面（领导者：Mrksich）。这些科学项目将在最高水平上进行，从而开发一系列新的合成方法，进而能够以高效、并行的方式生成约 20,000 种 20 毫克规模的新化合物。中心目标 2：培训下一代科学家，他们将开发高通量有机合成的新方法和策略。中心目标3：建立文库合成、表征和化学信息学的核心研究设施。该核心设施将拥有三个高度集成的组件：位于芝加哥大学的高通量合成组件、位于西北校区的Hit-to-Lead开发资源以及位于芝加哥伊利诺伊大学的化学信息学核心。目标 4：向生物学界提供广泛的宣传，从而能够快速有效地筛选新化合物库。除了为 NIH 路线图分子库计划提供新化合物外，我们还将与伊利诺伊州的三个主要高通量筛选中心以及许多单独的生物实验室合作。 CTCMLD 工作带来的连通性和协同作用的增强将代表芝加哥地区能力的重大进步，以及芝加哥学术界如何处理和解决化学、生物学和医学交叉领域问题的范式转变。

项目成果

Rapid, one-pot synthesis of β-siloxy-α-haloaldehydes.

• DOI: 10.1021/ja2066169
• 发表时间: 2011-09-14
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Saadi, Jakub;Akakura, Matsujiro;Yamamoto, Hisashi
• 通讯作者: Yamamoto, Hisashi

Super silyl stereo-directing groups for complete 1,5-syn and -anti stereoselectivities in the aldol reactions of beta-siloxy methyl ketones with aldehydes.

• DOI: 10.1021/ja101076q
• 发表时间: 2010-04-21
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Yamaoka Y;Yamamoto H
• 通讯作者: Yamamoto H

Palladium-catalyzed C3-benzylation of indoles.

• DOI: 10.1021/ja2095393
• 发表时间: 2012-01-11
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Zhu, Ye;Rawal, Viresh H.
• 通讯作者: Rawal, Viresh H.

Synthesis of an azide-tagged library of 2,3-dihydro-4-quinolones.

• DOI: 10.1021/jo9025447
• 发表时间: 2010-03-05
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Lee, Hajoong;Suzuki, Masato;Cui, Jiayue;Kozmin, Sergi A.
• 通讯作者: Kozmin, Sergi A.

Linking Cancer Metabolism to DNA Repair and Accelerated Senescence.

• DOI: 10.1158/1541-7786.mcr-15-0263
• 发表时间: 2016-02
• 期刊: Molecular cancer research : MCR
• 作者: Efimova EV;Takahashi S;Shamsi NA;Wu D;Labay E;Ulanovskaya OA;Weichselbaum RR;Kozmin SA;Kron SJ
• 通讯作者: Kron SJ