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

DNA编码文库细胞筛选平台的建立

• 批准号: 10646635
• 负责人: Thomas J. Kodadek
• 金额: $ 33.81万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10646635
• 关键词: Affect; Affinity; Agar; Anti-Bacterial Agents; Antibodies; Bacteria; Binding; Binding Proteins; Biological; Biological Process; Biology; Cells; Chemicals; Communities; Cytosol; DNA; Development; Diffuse; Eligibility Determination; Engineering; Equipment; Eukaryotic Cell; Fluorescein; Fluorescence; Future; Immobilization; Incubated; Individual; Laboratories; Libraries; Ligands; Link; Macrocyclic Compounds; Mainstreaming; Paper; Permeability; Phenotype; Plant Resins; Population; Proteasome Inhibitor; Proteins; Publishing; S phase; Solid; Stimulus; Structure; Surface; System; Technology; Tube; Update; Visual; Yeasts; cellular engineering; density; interest; irradiation; meter; microfluidic technology; multicatalytic endopeptidase complex; novel; screening; segregation; small molecule

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.

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DEL，每个分子都连接在一起， 编码DNA和文库是作为一个棘手的混合物产生的，还没有被 可用于功能和表型筛选。我们已经参与了 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， 珠子上的分子直接连接到DNA编码标签上。迄今为止， 一些论文描述了OBOC DEL的基于活动的屏幕， 需要使用高度复杂的微流体技术。该项目将 为OBOC DEL开发一个基于细胞的筛选平台， 专业设备。如果成功，这将使这种强大的方法， 生物活性分子的发现对化学生物学界来说更容易获得。