DNA Replication as a Target of Novel Antibacterial Drugs

DNA 复制作为新型抗菌药物的靶点

• 批准号: 6492200
• 负责人: Nebojsa JANJIC
• 金额: $ 10万
• 依托单位: REPLIDYNE, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2002-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6492200
• 关键词: DNA replication; Escherichia coli; antibacterial agents; bacterial DNA; chemical registry /resource; drug design /synthesis /production; drug resistance; fluorescent dye /probe; gene targeting; high throughput technology

DESCRIPTION (provided by applicant): Drug resistance among bacterial pathogens is becoming a serious health problem worldwide. Since the basic mechanism for resistance to many existing antibacterials is already widespread, the health care industry is currently in severe need of novel, mechanistically distinct antibacterials. To date, none of the commercially available antibacterials target any of the components of the replication system in bacteria. Since DNA replication is essential for the propagation of bacteria, such compounds would represent a novel class of antibacterial drugs. The overall aim of this project is to identify a diverse set of small molecules that inhibit targets within a replication system. A fluorescence-based assay will be set up in a high-throughput screening format in which synthesis of DNA is dependent on the coordinated function of 12 protein components of the E. coli replication apparatus. Initial screen will sample a chemical library consisting of approximately 5,000 molecules. For several most active compounds, in vitro potency will be established and targets within the replication system identified. This work will form the basis for an expanded screen of larger compound libraries and lead optimization of promising antibacterial drug candidates within the two-year phase II period. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（由申请方提供）：细菌病原体的耐药性 正在成为一个严重的全球性健康问题。由于基本机制， 对许多现有抗菌药物的耐药性已经很普遍， 护理行业目前迫切需要新颖的、机械上不同的 抗菌药到目前为止，没有一种市售抗菌药物 针对细菌复制系统的任何成分。由于DNA 复制对于细菌的繁殖是必不可少的，这样的化合物将 代表了一类新的抗菌药物。该项目的总体目标是 是识别一组不同的小分子，这些小分子可以抑制体内的靶点 复制系统基于荧光的测定将在 高通量筛选形式，其中DNA的合成依赖于 E.杆菌复制 设备.初始筛选将对化学文库进行采样，该化学文库由以下组成： 大约五千个分子对于几种最具活性的化合物，体外 将建立效价并在复制系统内靶向 鉴定这项工作将形成一个更大的扩展屏幕的基础 化合物库及先导化合物优化 在第二阶段的两年内，候选人。 拟议商业应用：不可用