Nerve agent testing

神经毒剂测试

• 批准号: 7235236
• 负责人: Douglas Mark Cerasoli
• 金额: $ 6.8万
• 依托单位: U.S. ARMY MEDICAL RESEARCH INST CHEM DEF
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7235236
• 关键词: enzymes; enzymes

The goal of the Organophosphorus Nerve Agent Testing (ONAT) Core, a component of the Center for Catalytic Bioscavenger Medical Defense Research, is to test the mutant enzymes produced by other Research Projects in the Center for in vitro and in vivo efficacy against organophosphorus (OP) nerve agents. The results from this testing will contribute directly to the development of a pretreatment that offers complete protection from poisoning by OPs. The core is located at the US Army Medical Research Institute of Chemical Defense, a singular national resource with a highly trained staff of scientists supported by safety, surety, and environmental specialists who ensure regulatory compliance of experiments involving highly toxic surety agents such as OP nerve agents. The mission of the USAMRICD is the development of medical countermeasures against chemical weapons, which is precisely aligned with the mission of the CounterACT initiative. The ONAT core is uniquely positioned to assess the function of anti-OP bioscavengers against bona fide nerve agents; the use of these highly toxic agents is restricted to a very limited number of research facilities worldwide. The tests to be conducted by the core will include characterization of the OP nerve agent reactivity, specificity, and stereoselectivity of candidate bioscavenger enzymes using a combination of colorimetric, calorimetric, and gas chromatographic/mass spectroscopy approaches. The capacity of different enzymes to persist in the circulation of a model test animal, and the protection from OP toxicity afforded by these enzymes will also be evaluated. The multidisciplinary approach of the ONAT core to assay development and efficacy testing will support the development of a 'next generation' bioscavenger molecule with the potential to bind and destroy OP nerve agents in the blood, before they distribute to the brain, central nervous system, and other toxic targets. In this regard it is important that the USAMRICD, and in particular the PI of the Center as well as the PI for this core component, have experience in both basic science and in early product development, meaning attention will constantly remain focused on not only the scientific issues, but also on the requirements to develop a novel, protein based drug product that will protect against the otherwise toxic effects of OP nerve agent exposure. The goal of the CounterACT program is to create new ways to protect ourselves from toxic chemicals like OP nerve agents. The goal of this core proposal is to test how well these new approaches defend against highly toxic nerve agents. Without the testing that will be conducted by this core, which is unique in its access to OP nerve agents, there will be no way to measure the effectiveness of these new approaches.

有机磷神经剂测试（ONAT）核心的目标，该中心的组成部分 催化Bioscavenger医疗防御研究是为了测试其他由其他人产生的突变酶 对有机磷（OP）神经的体外和体内功效中心的研究项目 代理商。该测试的结果将直接有助于开发提供的预处理 完全保护OP中毒。核心位于美国陆军医学研究所 化学辩护是一种单一的国家资源，拥有训练有素的科学家工作人员 安全，保证和环境专家，他们确保涉及实验的监管合规性 剧毒的保证代理，例如op神经剂。 USAMRICD的使命是发展 针对化学武器的医学对策，这与该化学武器完全一致 抵消倡议。 ONAT核心是独特的位置，可以评估抗OP的功能 对抗真正的神经毒剂的生物可能助剂；这些剧毒毒剂的使用仅限于 全球研究设施数量有限。核心要进行的测试将包括 候选Bioscavenger的操作神经剂反应性，特异性和立体选择性的表征 使用比色法，量热和气相色谱/质谱的酶 方法。不同酶在模型测试动物的循环中持续存在的能力， 这些酶提供的保护免受OP毒性的保护也将得到评估。多学科方法 ONAT核心的测定开发和功效测试将支持下一步的开发 生成的生物库分子具有结合和破坏血液中的op神经的潜力， 在它们分发到大脑之前，中枢神经系统和其他有毒靶标。在这方面是 重要的是USAMRICD，尤其是中心的PI以及该核心的PI 组成部分，在基础科学和早期产品开发方面都有经验，这意味着关注将会 不仅要不仅专注于科学问题，而且还关注开发小说的要求， 基于蛋白质的药物，可以防止接触神经剂暴露的原本有毒作用。 反对计划的目的是创建新的方法来保护自己免受诸如诸如的有毒化学物质 神经毒剂。该核心提议的目的是测试这些新方法的防御能力 剧毒神经剂。没有该核心将进行的测试，这在其上是独一无二的 进入op神经剂，将无法衡量这些新方法的有效性。