University of Kansas Specialized Chemistry Center

堪萨斯大学（KU）在合成药物化学方面有着成功的历史，并一直持续到今天。NIH在这些活动中的投资包括化学方法学和图书馆发展（CMLD）中心和试点规模图书馆赠款。在强大的机构支持下，包括一个专门用于探测发现的新建筑，我们建议将这些资源作为专业化学中心（SCC），为MLPCN服务。KU SCC的目标是每年合成10-15个探针候选物集合，每组包含20 mg数量的100-300个离散化合物，通过HPLC（UV或ESL检测）测定的化学纯度>90%。在过去的15个月里，我们向MLSCN提交了超过1600种符合这些要求的化合物，其中包括十几种不同的化学型。因此，我们已经在与SCC倡议所需的水平相当的水平上运作，并制定了一项现实的计划，以迅速应对优化MLPCN伙伴关系所获得的命中率的挑战。拟议计划的优势包括：（1）已证明有能力生产MLPCN所需数量和纯度的小分子;（2）如何将化合物有效地交到生物合作者手中的实用知识，（3）在与生物合作者合作以及优化化合物效力和先导化合物选择性方面具有专业知识（以及一组优秀的顾问，他们将每月提供指导），（4）平行合成技术的实践经验和图书馆制作的优秀基础设施，（5）分配到一个全新的实验室，该实验室位于一个新的建筑扩建部分，其中包括11个通风柜，专门用于合作生物医学发现（实验室将于2008年4月完成），（6）强大的化学信息学专业知识，（7）经验丰富的PI和现有的行政结构，将促进项目活动的协调，（8）匹配资金，为SCC提供必要的主要设备并建立必要的实验室，以及（9）对MLSCN的承诺。 一个中心为基础的研究项目，提出了解决问题的细胞内目标识别的小分子探针，在生物医学研究中的一个公认的障碍。本项目的目标是：（1）开发使用荧光分子探针可视化和鉴定细胞内蛋白质靶点的方法;（2）开发酵母三杂交（Y3 H）系统，作为鉴定小分子蛋白质靶点的工具。

The University of Kansas (KU) has a history of success in synthetic medicinal chemistry that continues to the present day. NIH investments in these activities have included a Chemical Methodologies and Library Development (CMLD) center and a Pilot Scale Library grant. With strong institutional support including a new building dedicated to probe discovery, we propose to marshal these resources in the service of the MLPCN as a Specialized Chemistry Center (SCC). The goals of the KU SCC will be to synthesize 10-15 collections of probe candidates per year, with each set containing between 100-300 discrete compounds in 20 mg quantities and >90% chemical purity as determined by HPLC (UV or ESL detection). In the past 15 months, we submitted over 1600 compounds that met these requirements to the MLSCN, comprising about a dozen different chemotypes. Thus, we are already functioning at the level comparable to that required for the SCC initiative and have developed a realistic plan for quickly undertaking the challenge of optimizing hits obtained from the MLPCN partnership. Strengths of the proposed program include (1) the demonstrated capability of producing small molecules in the quantities and purities demanded by MLPCN; (2) practical know-how of how to get compounds efficiently into the hands of biological collaborators, (3) demonstrated expertise in working with biological collaborators and optimizing compound potency and selectivity of a lead compound (and an outstanding set of consultants who will provide guidance on a monthly basis), (4) practical experience with parallel synthesis techniques and outstanding infrastructure for library production, (5) assignment to a brand-new laboratory containing 11 hoods in a new building extension that is dedicated to collaborative biomedical discovery (labs to be completed in 4/08), (6) strong cheminformatics expertise, (7) an experienced PI and an existing administrative structure that will facilitate the coordination of the project activities, (8) matching funds to provide essential major equipment and set up necessary laboratories for the SCC, and (9) a demonstrated commitment to the MLSCN. A Center-based research project is proposed to address the question of intracellular target identification for small molecule probes, an acknowledged roadblock in biomedical research. The goals of this project will be to (1) develop methodology for visualizing and identifying intracellular protein targets using fluorescent molecular probes and (2) develop yeast three-hybrid (Y3H) systems as tools for the identification of protein targets of small molecules.