Chemistry Core

化学核心

• 批准号: 10592384
• 负责人: TIMOTHY S BUGNI
• 金额: $ 103.58万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592384
• 关键词: Chemistry; Core

Project Summary The ability of microbes, especially bacteria, to produce biologically active molecules that can form the basis of therapeutic agents to confront important human pathogens forms the overall premise of this CETR application. The microbial producers will be symbiotic bacteria from a variety of niches. The assays that will lead to the discovery of potential therapeutic agents will focus on multidrug resistant Gram-negative bacteria and systemic fungal pathogens. The Chemistry Core will be responsible for converting the activity discovered in biological assays into purified active molecules with known structures in sufficient amounts that secondary functional assays, structure-activity studies, and target identification can be addressed. This overall goal will be accomplished with four tasks, which are described in much greater detail in a later section of the proposal. Task 1: Produce symbiotic microbe metabolite fractions for dereplication and in vitro efficacy and safety testing. Task 2: Scale-production of promising fraction for in vivo testing and structural elucidation. Task 3: Purify and structurally characterize the active molecule/s. Task 4: Large-scale production for advanced in vivo PK/PD and mechanism of action determination.

项目摘要 微生物，尤指细菌，产生生物活性分子的能力，这些分子可形成 对抗重要的人类病原体的治疗剂形成了该CETR应用的总体前提。 微生物生产者将是来自各种生态位的共生细菌。将导致 潜在治疗剂的发现将集中在多重耐药革兰氏阴性菌和全身性 真菌病原体化学核心将负责将生物学中发现的活性转化为 测定具有已知结构的纯化的活性分子的量， 分析、结构-活性研究和靶标鉴定。这一总体目标将是 这一进程将通过四项任务来完成，提案后面一节将更详细地介绍这四项任务。 任务1：生产共生微生物代谢物组分，用于去复制和体外功效和安全性 试验. 任务2：用于体内测试和结构解析的有希望的级分的规模生产。 任务3：纯化并结构表征活性分子。 任务4：大规模生产，用于先进的体内PK/PD和作用机制测定。