Exploring the solution and surface chemistry of peptides and proteins

从宏观到微观的分子组成，生物结构都是非常有序的，因此表现出一些非常有趣的性质。我们建议通过在分子水平上对生物系统进行受控模仿来利用这些特性。我们准备解释分子自组装的复杂决定因素以及这些因素如何影响溶液和表面性质和行为等因素，并开发新的技术工具从基本观点评估这些分子。 在这个资助周期中，我的团队将联合收割机合成和分析实验相结合，以全面解决主要的知识差距，并建立一个新的基础，了解化学修饰如何影响生物分子相互作用。我们将通过探索蛋白质和肽的化学修饰及其在溶液和表面上的结构，功能和性质来实现这一目标。我们还想了解如何操纵和利用各种应用程序的系统属性。该计划将在以下方面取得重大进展：1）开发控制肽特性的化学工具，2）鉴定具有潜在生物传感器应用的新型蛋白质平台，3）为肽和蛋白质科学的新发现建立技术和分析方法。 总的来说，这些努力将合并溶液和表面数据，以解释迄今尚未解决的肽和蛋白质相互作用和性质的基本机制。这些创新的扩展将为跨物种（如真核生物和细菌）的生物分子的理论和实验研究带来新的方法。在分子和大分子尺度上操纵生物分子的化学策略的发展将导致更可控的生物材料和生物传感器技术，以应对环境，生物医学和工业挑战。它们也将被科学家用于现场和实验室环境，例如精确测量分子的浓度和命运，或制造具有所需特性的生物材料。 除了我们成熟的电化学和MS分析工具外，这些发现与加拿大环境和卫生部门具有经济相关性，其商业化和实施将带来切实的社会效益并创造就业机会。这项工作将在多个层面上培训HQP，进行强有力的科学调查，并应用新方法来解决以前难以解决的科学问题。

From the macroscopic down to the microscopic individual composition of molecules, biological structures are extremely well-ordered and, as a result, exhibit some very interesting properties. We propose to harness these properties through controlled mimicry of biological systems at a molecular level. We are poised to explain the complex determinants of molecular self-assembly and how these influence factors like solution and surface properties and behaviours, as well as to develop novel technological tools for evaluation of these molecules from the fundamental point of view. During this grant cycle, my team will combine synthetic and analytical experiments to comprehensively address major knowledge gaps and establish a new basis for understanding how chemical modifications influence biomolecular interactions. We will achieve this through exploration of chemical modifications of proteins and peptides and their structure, function and properties in solution and on surfaces. We also want to understand how to manipulate and exploit system properties for various applications. The proposed program will make major advances in: 1) development of chemical tools for controlling peptide properties, 2) identification of novel protein-based platforms with potential biosensor applications, and 3) establishing technologies and analytical methodologies for new discoveries to be made in peptide and protein sciences. Collectively, these efforts will merge solution and surface data to explain fundamental mechanisms governing peptide and protein interactions and properties that to date have gone unresolved. The extension of these innovations will lead to new ways to theoretically and experimentally study biomolecules across species, such as eukaryotes and bacteria. The development of chemical strategies to manipulate biomolecules at molecular and macromolecular scales will lead to much more controlled biomaterial and biosensor technologies to address environmental, biomedical and industrial challenges. They will also be used by scientists in the field and laboratory settings, for example for accurately measuring concentrations and fates of molecules, or fabricating biomaterials with desired properties. Alongside our established electrochemical and MS analytical tools, these discoveries are economically relevant to Canadian environment and health sectors, and their commercialization and implementation will lead to tangible societal benefits and create employment opportunities. This work will train HQP, at multiple levels, in robust scientific investigations, and the applications of novel approaches to address previously intractable science questions.