Core--Medicinal chemistry: discovery and screening

活性氧（ROS）和线粒体的清道夫！一氧化氮合酶（mtNOS）抑制剂在开发新型口服放射保护剂和缓解剂中起着关键作用。核心有两个相互依存和整合的部分：(a)药物（发现）化学，和(b)药理学评估和配方。核心医学（发现）化学部分的总体目标是提供新颖的、化学可逆的、因此是定时释放的药物。核心药理学部分的总体目标是为体外高通量筛选化学文库提供资源，为新合成化合物的细胞活性提供初步评估，并为CMCR项目和核心进行配方和稳定性研究。我们有五个具体任务：

Scavengers of reactive oxygen species (ROS) and mitochondria! nitric oxide synthase (mtNOS) inhibitors play a key role in the development of novel orally administrable radioprotectants and mitigators. The Core has two interdependent and integrated Sections: (a) Medicinal (Discovery) Chemistry, and (b) Pharmacological Evaluation and Formulation. The overall goal of the Medicinal (Discovery) Chemistry section of the Core is to provide novel, chemoreversible and thus timed-release agents. The overall goal of the Pharmacology Section of the Core is to provide resources to allow in vitro high throughput screening of chemical libraries, to provide an initial evaluation of the cellular activity of newly synthesized compounds, and to conduct formulation and stability studies for the CMCR Projects and Cores. We have five specific tasks: 1. Preparation of peptide mimetics based timed-release derivatives of ROS scavengers (TEMPO derivatives) and mtNOS inhibitors. These agents will be cell-permeable and membrane-targeted. 2. Synthesis of cell-permeable peptide antioxidants specifically targeted to the inner mitochondrial membrane. 3. Implementing automated high throughput screening assays. 4. Conducting multiparametric analyses of newly synthesized compounds in intact cells. 5. Formulating compounds for in vivo intravenous and oral use, evaluating chemical extraction methods to prepare the samples for analytical analysis, and determine compound stability in aqueous and biological fluids.