Chicago Tri-Institutional Center for Chemical Methods and Library Development

描述（由申请人提供）：我们向NIH申请的主要目的是建立芝加哥三机构化学方法和文库开发中心（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，这将显著促进用于广泛生物筛选的小分子文库的开发。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，以匹配NIH的资金。CTCMLD将有以下几个主要目标。中心目标1：开展四个高度综合的项目，旨在显著促进化学多样性的产生和高质量小分子库的组装。这四个拟议的项目是：（a）新的氮基杂环库的实用合成（领导者：Scheldt和Gevorgyan）;（B）聚酮化合物文库的多组分组装（领导者：Yamamoto）;（c）组装支架无偏小分子文库（领导人：Kozmin）;以及（d）为新反应开发、小型化库合成和小分子固定化开发定制表面（领队：Mrksich）.科学项目将在最高水平上进行，从而开发出一系列新的合成方法，从而能够以高效、平行的方式产生约20，000种20 mg规模的新化合物。中心目标2：培养下一代科学家，他们将开发高通量有机合成的新方法和策略。中心目标3：建立库合成、表征和化学信息学的核心研究设施。核心设施将有三个高度集成的组件：位于芝加哥大学的高产量合成组件，位于西北校区的命中领导开发资源和位于芝加哥的伊利诺伊大学的化学信息学核心。目标4：向生物界提供广泛的外联活动，以便能够快速有效地筛选新的化合物库。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和许多独立的生物实验室合作。CTCMLD的工作所带来的连通性和协同作用的增加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，生物学和医学界面问题的范式转变。

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.