Bringing Modern Circular Dichroism Instrumentation to Notre Dame Researchers

描述（由申请人提供）：蛋白质构象变化的表征是在分子水平上理解生物学功能的关键先决条件。几十年来，圆二色谱（CD）光谱一直是生物物理工具箱的重要组成部分，利用小分子，蛋白质和核酸的手性特性提供分子结构及其变化的信息。例如，由蛋白质解折叠（由诸如温度或pH的扰动诱导）或折叠（由小分子配体、蛋白质或核酸的结合诱导）引起的二级结构的变化可以快速且容易地定量为远UV CD光谱的变化。另外，CD光谱也是研究小分子手性选择性的重要技术，包括药物，荧光染料和旨在模拟酶催化的化学催化剂。在过去的十年中，仪器光学的进步，以及其他功能的发展，如同步荧光检测，并与停流动力学设备的无缝集成，进一步提高了CD光谱的生物医学研究的效用。该提案是对计划公告PAR-09-028的回应，要求提供资金购买最先进的CD分光偏振仪，以进一步实现圣母大学科学家的研究目标。这台仪器将取代我们目前的卡里/阿维尼翁仪器，尽管该仪器在超过25年的使用寿命中仍然有效并得到精心维护，但现在光学和电子设备已经过时。新仪器将被安置在最近翻新和扩建的核心设施中，代表了目前正在进行的扩大和改善圣母大学研究基础设施的巨大努力之一。因此，该仪器的监督，护理和维护通过核心设施工作人员的扩大创造就业机会，而获得这种最先进的研究设备将继续增加研究企业在圣母院的努力。

DESCRIPTION (provided by applicant): Characterization of protein conformational changes is a crucial pre-requisite to understanding biological functions on a molecular level. Circular dichroism (CD) spectroscopy has been an essential component of the biophysical tool kit for decades, exploiting the chiral properties of small molecules, proteins and nucleic acids to provide information on molecular structure and its changes. For example, changes in secondary structure caused by protein unfolding (induced by perturbants such as temperature or pH), or folding (induced by the binding of a small molecule ligand, protein, or nucleic acid) can be quickly and easily quantified as changes in the far-UV CD spectrum. Separately, CD spectroscopy is also an essential technique in the study of chiral-selective properties of small molecules, including drugs, fluorescent dyes, and chemical catalysts designed to mimic enzymatic catalysis. Over the past decade, advancements in instrument optics, as well as the development of additional functionalities such as simultaneous fluorescence detection, and seamless integration with stopped-flow kinetic devices, have further enhanced the utility of CD spectroscopy for biomedical studies. This proposal, in response to Program Announcement PAR-09-028, requests funds to purchase a state-of-the-art CD spectropolarimeter to further the research goals of University of Notre Dame scientists. This instrument will replace our current Cary/Aviv instrument, which although still productive and carefully maintained for its >25 years of life, is now optically and electronically obsolete. The new instrument will be housed in a recently renovated and expanded core facility, and represents one piece of a large effort currently underway to expand and improve research infrastructure at the University Of Notre Dame. As such, supervision, care and maintenance of this instrument create employment opportunities through core facility staff expansion, while access to this state-of-the-art research equipment will continue to grow the research enterprise efforts at Notre Dame.