New Chemistry from Biology with Bioinorganic Chemistry

生物学与生物无机化学的新化学

• 批准号: RGPIN-2019-05470
• 负责人: Bohle, David
• 金额: $ 3.5万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689706
• 关键词: New; Chemistry; Biology; Bioinorganic

Although there are many motivations and definitions of chemical biology the one that drives the program of research in my laboratory is that it is a theme and an approach "to discover new chemistry." Our unifying guiding hypothesis is global, open-ended, and invigorating; by understanding how biological evolution has circumvented the fundamental chemical limitations imposed by terrestrial temperature, pressure, environment, and element distribution considerable new chemistry can be discovered. This approach allows for discovery and innovation in that not only are new techniques and tools used, and developed, to help solve important health related problems, but solutions to deeper scientific issues are uncovered. Current chemical biology research in the Bohle group follows three general themes: A; the first is related the unusual biochemistry often employed by parasites, with the heme metabolism in pathogens such as plasmodia (malaria), B; the bioinorganic chemistry of rarely utilized elements such as arsenic and tungsten, and C; the final area to the study of bio-inspired nitrogen chemistry. A. Parasites such as plasmodia have a highly evolved biology which allows them to have some of the most complicated life cycles and often have elegant biochemistry. Often they have sophisticated means to circumvent the host's immune system; they are a logical place to apply the ideas of chemical biology. B. The biochemistry of underutilized elements remains a challenging area of chemical biology. Elements such as tungsten and arsenic are in fact relatively common and available, and yet evolution has rarely used either of them in any context. Our research into these topics is highly collaborative and at present focusses on their toxicology and medicinal value. Finally C, few first row elements have the remarkably variable oxidation state chemistry of nitrogen and its oxides. If we can understand how the nitrogen oxides are employed in organisms we can in principle use these ideas in commercial/industrial settings especially for pollution abatement strategies. ***Our approach to this research is to work on the fundamental problems in each of these themes. This style is ideally suited for the training of HQP and it does not tie us to a particular technique, method, or class of compounds. To illustrate this diversity my group can frequently be found working at Synchrotrons as well as preparing and characterizing new compounds. For the latter we use a wide range of spectroscopic and structural techniques, with X-ray diffraction being particularly useful. Theoretical methods are also drawn upon for both their predictive and supporting roles. At its best our work is highly collaborative with our chemistry having value for biologists and clinicians as well stimulating our efforts in bioinorganic chemical biology.**

尽管化学生物学有许多动机和定义，但在我的实验室中推动研究计划的一种动机和定义是，它是一种主题和一种“发现新化学反应”的方法。我们统一的指导假设是全球性的，开放的和令人振奋的。通过了解生物进化如何规避陆地温度，压力，环境和元素分布所施加的基本化学限制，可以发现大量的新化学反应。这种方法允许发现和创新，因为不仅是使用并开发的新技术和工具来帮助解决重要的健康问题，而且还发现了更深入的科学问题的解决方案。 Bohle组的当前化学生物学研究遵循三个一般主题：A；第一个与寄生虫经常使用的异常生物化学有关，与疟原虫（疟疾），b等病原体中的血红素代谢相关。很少利用砷和钨的生物无机化学，以及C；生物启发的氮化学研究的最终区域。 A.寄生虫（例如疟原虫）具有高度进化的生物学，使他们能够拥有一些最复杂的生命周期，并且经常具有优雅的生物化学。 通常，他们具有精致的手段来规避宿主的免疫系统；它们是应用化学生物学思想的逻辑场所。 B.未充分利用元素的生物化学仍然是化学生物学的挑战性领域。 钨和砷之类的元素实际上相对普遍且可用，但是在任何情况下，进化都很少使用它们。 我们对这些主题的研究是高度协作的，目前将其重点放在其毒理学和药物价值上。 最后，C，很少有第一行元素具有氮及其氧化物的氧化状态化学差异很大。 如果我们能够理解如何在有机体中使用氮氧化物，那么我们可以原则上在商业/工业环境中使用这些想法，尤其是用于减少污染策略。 ***我们对这项研究的方法是解决这些主题中每个主题的基本问题。 这种样式非常适合对HQP的培训，并且不将我们与特定的技术，方法或类化合物联系起来。 为了说明这种多样性，我的小组经常可以在同步基因上工作，并准备和表征新化合物。 对于后者，我们使用各种光谱和结构技术，X射线衍射特别有用。 还为其预测性和辅助角色绘制了理论方法。 最好的工作与我们的化学具有对生物学家和临床医生有价值的化学作用，以及刺激我们在生物无机化学生物学方面的努力。********