Freeze-dryer console

冷冻干燥机控制台

• 批准号: 390324-2010
• 负责人: Tsantrizos, Youla
• 金额: $ 2.62万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments - Category 1 (<$150,000)
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=443163
• 关键词: Freeze; dryer; console

One of our key objectives is to develop robust synthetic methodologies that are amenable to high throughput parallel synthesis of compounds that will serve as tools in investigations of complex networks of bimolecular interactions. Currently, we are focusing on the design and synthesis of heterocyclic and peptidomimetic scaffolds that can selectively modulate the catalytic activity of human farnesyl pyrophosphate synthase (hFPPS) in vitro, in cell-based assays and in animal models. The hFPPS enzyme occupies a strategic location at the first committed step of the mevalonate pathway leading to protein prenylation of the Ras oncogenic proteins. In addition, this enzyme is implicated in the interferon-induced innate immune response against viral infections in humans. Therefore, hFPPS plays a crucial role at a cross-over point between the host's metabolism, oncogenesis and innate immunity. Studies in this area require the synthesis of numerous compounds which must be purifies by reversed phase HPLC and subsequently lyophilized to dryness. The requested Freeze-Dryer instrument is a key component within a cluster of instruments required for the success of our research program. This cluster of instruments is essential in achieving the efficiency and throughput of compound preparation that is needed in order to thoroughly investigate the interactions between hFPPS and its active site inhibitors, as well as the interactions between hFPPS and the host factor viperin, in vitro and in cell-based biological assays.

我们的主要目标之一是开发适合于高通量并行合成化合物的稳健的合成方法，这些方法将作为研究双分子相互作用的复杂网络的工具。目前，我们正致力于设计和合成能够在体外、细胞和动物模型中选择性地调节人法尼基焦磷酸合成酶(HFPPS)催化活性的杂环和仿肽支架。HFPPS酶在甲氧丙戊酸途径的第一步中占据重要位置，导致RAS癌基因蛋白的蛋白质预烯基化。此外，这种酶与干扰素诱导的针对人类病毒感染的先天免疫反应有关。因此，hFPPS在宿主新陈代谢、肿瘤发生和先天免疫的交叉点上起着至关重要的作用。这方面的研究需要合成许多化合物，这些化合物必须用反相高效液相色谱法进行纯化，然后冷冻干燥至干燥。所要求的冻干机仪器是我们研究计划成功所需的一系列仪器中的关键部件。这一组仪器对于实现化合物制剂的效率和吞吐量至关重要，为了在体外和基于细胞的生物检测中深入研究hFP PS与其活性部位抑制剂之间的相互作用，以及hFP PS与宿主因子Viperin之间的相互作用。