Establishment of a Cell-Based Screening Platform for DNA Encoded Libraries

项目摘要 DNA编码库(Del)技术彻底改变了蛋白质的发现-- 结合小分子。然而，传统的DELS，在那里每个分子都是相连的 一种编码DNA的文库是作为一种难以处理的混合物产生的，还没有 对功能性和表型筛选很有用。我们已经参与了 功能性一珠一剂(OBOC)DELS的研制 和基于细胞的屏幕，因为珠子是可分离的，并且只有一小部分 珠子上的分子直接连接到DNA编码标签上。到目前为止，非常小的 描述OBOC DELS基于活动的屏幕的报纸数量已经 需要使用高度复杂的微流控技术。这个项目将 为OBOC DELL开发基于细胞的筛查平台，不需要任何 专门的设备。如果成功，这将使这种强大的方法 生物活性分子的发现更容易为化学生物界所接受。

Project Summary DNA-encoded library (DEL) technology has revolutionized the discovery of protein- binding small molecules. However, traditional DELs, where every molecule is connected to an encoding DNA and the library is produced as an intractable mixture, have not been useful for functional and phenotypic screening. We have been involved in the development of one bead one compound (OBOC) DELs, which can be used for functional and cell-based screens since beads are separable and only a small percentage of the molecules on the beads are linked directly to a DNA encoding tag. To date, the very small number of papers that have described activity-based screens of OBOC DELs have required the use of highly sophisticated microfluidics technology. This project will develop a cell-based screening platform for OBOC DELs that will not require any specialized equipment. If successful, this will make this powerful approach to the discovery of bioactive molecules far more accessible to the chemical biology community.