University of Pittsburgh Center for Chemical Diversity

化学方法学和图书馆发展卓越中心的总体目标是 应用是在以下领域进行的原始研究的基础上生成新的化学库： 新型肽类药物的合成和分析（项目1）， 多样性导向的合成和战略分离（项目2），以及开发和实施 氟聚合物微反应器（项目3）。我们的项目将开发新的分离技术 利用氟相合成策略，设计和开发纳米级高度并行的微反应器 有机合成，并发现新的手性液相色谱固定相。每个项目 有两个阶段：研究和应用。在研究阶段，新的方法将在 个人研究小组。在发展阶段，一个集中的设施，面向多样性的综合 (DOS)方便访问最先进的自动化合成、分离和分析的核心 设备，将验证方案和放大库合成，以访问500- 10，000个电子化合物 每个图书馆。这种安排将为所有新方法提供真正独立的验证， 具有即时的“真实的世界”反馈的项目的实用性和实用性。严格的质量控制意志 确保高纯度的样品，将与生物领域的合作者共享。该化合物 库，预计最终将由10-20 mg中超过50，000个结构多样的样品组成 数量，也将获得来自工业和制药业的外部当事人。 虽然学术实验室已经开发了许多新的方法来进行图书馆综合， 在图书馆生产和分析的有效自动化方面，他们实际上还达不到要求。 producinglibraries图书馆and making制造them accessible访问to nonspecialized非specialized专业labs实验室.我们的中心计划将解决 这一缺陷，并实现一个新的范式，在研究验证和图书馆规模扩大。它结合了 学术研究和创新的力量在化学与自动化合成的尖端工具， 分析和分离的综合，跨学科的方式，包括微型设备 development发展and biological生物screening筛选.

The overall goal of this Center of Excellence in Chemical Methodologies and LibraryDevelopment grant applicationis to generate novel chemical librariesbased on originalresearch carried out in the areas of synthesisand analysis of novel peptidemimetics (Project 1), the combinationof innovativemethodsfor diversity-orientedsynthesis and strategicseparations (Project 2), and the developmentand implementation of fluoropolymer-based microreactors(Project 3). Our Programwill develop new separationtechnologies usingfluorous phase synthesisstrategies, design and develop microreactorsfor nano-scale highly parallel organicsynthesis, and discover new chiralstationary phases for liquidphase chromatography. Each Project has two stages: research and application. At the research stage, new methodologieswill be developed in individualresearch groups. At the development stage, a centralized facility, the Diversity-OrientedSynthesis (DOS) Core with convenient access to state-of-the-art automated synthesis,separation, and analysis equipment, will validate the protocolsand scale-up library synthesisto access 500-10,000 singlecompounds per library. This arrangement will provide trulyindependent validationfor all new methodologiesand provide the Projectswith immediate "real world" feedback of utilityand practicality. Rigorousquality controlwill ensure high purity samples that will be shared with collaborators inthe biologicalfields. This Compound Library, envisionedto be composed of ultimately>50,000 structurallydiverse samples in 10-20 mg quantities,will also be accessible to outsidepartiesfrom industry and academe. While academic labs have developed many new methodsfor library synthesisand contributedimportant insightstoward efficient automation for library productionand analysis, they have fallen short in actually producinglibrariesand making them accessibleto non-specialized labs. Our Center Programwill address this deficiencyand realize a new paradigm in research validationand library scale-up. It combinesthe power of academic research and creativityin Chemistry with cutting-edgetools of automation in synthesis, analysis, and separation in an integrated, interdisciplinarymanner that includesmicroscaledevice developmentand biologicalscreening.