EQUIPMENT FOR "ACCURATE CONSTANT VIA TRANSIENT INCOMPLETE SEPARATION"

要求设备。我的研究是由现代药物发现的惊人问题驱动的：非常低的成功率和飙升的成本，主要是由于缺乏用于识别和表征药物先导物的高能力技术。我的小组最近公布了该领域的两项重大突破：一种比目前使用的效率高一千万倍的药物铅识别技术（新）。化学。Int。编辑。2019,58,27392743)，以及唯一固有准确的药物先导物表征技术，绰号为ACTIS (Angew。化学。Int。编辑。2019,58,66356639)。从概念上讲，ACTIS是基于一种新型的快速和简单的分子大小不同的分离。目前的拨款申请要求为采购ACTIS设备提供支持。拟议的设备将是我们的主要研究工具，其100%的能力将被我们和我们的合作者利用。***所需设备支持的研究活动。该仪器将用于在三个领域取得重大技术进步。第一个领域是验证经典小分子药物的药物先导。第二个领域是生物制药的验证，这是从细菌和细胞中获得的大分子药物。第三个领域是研究在生物和技术上重要的不同分子之间形成的非共价复合物。这三个领域的研究是由公认的小分子药物和生物制药开发技术的不足以及用于研究生物分子相互作用的研究工具所推动的。我的研究项目是建立在多个外部支持的研究项目之上的，这些项目是许多学术团体、制药公司和医院共同努力的结果。***研究活动为何重要，对谁重要。预期的结果将通过简化药物开发的早期阶段使加拿大制药公司受益。这也将有利于加拿大公司开发基于生物分子相互作用的诊断工具。最终，这些成果将有利于加拿大经济和加拿大人，他们将更早、更低成本地获得新的药物和新的疾病检测方式。拟议设备支持的研究涉及各级受训者：本科生、研究生和博士后。这将为他们提供一个独特的机会，获得组装、维护和操作先进分析仪器的宝贵实践经验。所获得的技能与现代制药工业和医院分子病理学实验室高度相关。***延迟购置所要求设备的影响。如果无法获得提议的设备，我的高效率研究计划将会中断，我的研究生和博士后将无法完成他们的训练

Requested equipment. My research is driven by alarming problems of modern drug discovery: very low success rates and sky-rocketing costs largely caused by the absence of highly-enabling technologies for identification and characterization of drug leads. My group has recently disclosed two major breakthroughs in this field: a drug-lead identification technology which is ten million times more efficient than the currently used one (Angew. Chem. Int. Ed. 2019, 58, 27392743), and the only inherently accurate drug-lead characterization technology, which is nicknamed ACTIS (Angew. Chem. Int. Ed. 2019, 58, 66356639). Conceptually, ACTIS is based on a new type of fast and simple separation of molecules which differ in size. The present grant application requests support for acquiring equipment for ACTIS. The proposed equipment will be our main research tool, and 100% of its capacity will be utilized by us and our collaborators.***Research activities to be enabled by requested equipment. The instrument will be used to make major technological advances in three areas. The first area is validation of drug leads for classical small-molecule drugs. The second area is validation of biopharmaceuticals, which are large-molecule drugs obtained from bacteria and cells. The third area is the study of non-covalent complexes formed between different molecules of biological and technological importance. The research in these three areas is motivated by well-recognized deficiencies of technologies available for development of small-molecule drugs and biopharmaceuticals as well as research tools utilized to study biomolecular interactions. My research program is built upon multiple externally supported research projects that are collaborative efforts of many academic groups, pharmaceutical companies, and hospitals.***Why and to whom the research activities are important. The expected outcomes will benefit Canadian pharmaceutical companies by streamlining early stages of drug development. They will also benefit Canadian companies developing diagnostic tools based on biomolecular interactions. Eventually, the outcomes will benefit the Canadian economy and Canadians who will be receiving new drugs and new modalities of disease detection earlier and at lower costs. The research supported by the proposed equipment involves trainees at all levels: undergraduate students, graduate students, and postdoctoral fellows. It will provide them with a unique opportunity to gain valuable hands-on experience with assembling, maintaining and operating advanced analytical instrumentation. The skills to be obtained are highly relevant to the modern pharmaceutical industry and molecular-pathology labs of hospital.***Impact of a delay in acquisition of the requested equipment. The inability to obtain the proposed equipment will stall my highly productive research program and stop progress of my graduate students and postdoctoral fellows towards completion of their training.**