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

项目概要 DNA 编码文库 (DEL) 技术彻底改变了蛋白质的发现 结合小分子。然而，传统的 DEL 中每个分子都是相连的 编码 DNA 和文库是作为难以处理的混合物产生的，尚未被 可用于功能和表型筛选。我们曾参与过 开发一珠一化合物 (OBOC) DEL，可用于功能性 和基于细胞的筛选，因为珠子是可分离的，并且只有一小部分 珠子上的分子直接与 DNA 编码标签相连。迄今为止，规模非常小 描述基于活动的 OBOC DEL 屏幕的论文数量 需要使用高度复杂的微流体技术。该项目将 为 OBOC DEL 开发基于细胞的筛选平台，不需要任何 专业设备。如果成功的话，这将使这种强有力的方法 化学生物学界更容易发现生物活性分子。

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.