Circular Dichroism Spectropolarimeter with fluorescence acquisition and temperatu

描述(由申请人提供)：在由NIH资助的核心项目中，圆二色谱(CD)旋光仪为了解蛋白质构象和展开、伴随多肽-膜相互作用和插入的构象转变、开发免疫原性较低、更有效的治疗性蛋白质制剂，以及发现难溶抗癌药物的替代制剂的动态方面提供了一个独特的窗口。我们寻求获得一台最先进的CD光谱偏振仪来支持和加强这些研究计划。这一工具将为分布在该区域地理区域的三所大学校园中的一所提供便利的途径，接触到得到良好支持但服务不足的调查组。仪器上的特定附件将使独特的实验方法成为可能，例如编程重复、同时分析多个样品、编程热斜坡研究以探测大分子构象、获取与CD测量交错的荧光发射数据，以及包括用于变性/复性研究的自动滴定仪。这些能力将极大地增强现有的NIH支持的项目。该仪器将由药学仪器设施运营，该设施自1995年以来一直运作成功，当时它将第一台共享访问CD仪器带到了纽约西部地区。该设施为来自布法罗大学(UB)的用户提供了开放访问，该大学是我们的地区合作伙伴罗斯威尔公园癌症研究所。和Hauptman-Woodward Research Inst.(HWI)，以及偶尔使用当地大学的用户。目前的活跃用户群约为24个实验室小组，其中大部分是由NIH资助的。该设施还提供专业人员培训和协助新用户，或与不太频繁的用户进行协作工作。与这一设施和提议有关的教职员工还包括研究生课程中与光盘有关的教学，为研究生和博士后实习生提供光盘理论的坚实基础以及光盘在其研究项目中的潜在应用。

DESCRIPTION (provided by applicant): In the NIH-supported core projects conducted by the eight co-investigators of this proposal, Circular Dichroism (CD) spectropolarimetry provides a unique window into dynamic aspects of protein conformation and unfolding, conformational transitions accompanying peptide-membrane interaction and insertion, the development of less immunogenic, more effective therapeutic protein formulations, and the discovery of alternative formulations for poorly-soluble anticancer drugs. We seek to acquire a state-of-the-art CD spectropolarimeter to support and enhance these research programs. This instrument will provide convenient access to a well-supported but under-served group of investigators on one of three university campuses that are spread across this regional geographic area. Specific accessories on the instrument will make possible unique experimental approaches, such as programmed repetitive, simultaneous analysis of multiple samples, programmed thermal ramping studies to probe macromolecule conformation, acquisition of fluorescence emission data interleaved with CD measurements, and inclusion of an automated titrator for denaturation/refolding studies. These capabilities will enhance greatly the existing NIH-supported projects. The instrument will be operated by the Pharmaceutical Sciences Instrumentation Facility, which has operated successfully since 1995, when it brought the first shared-access CD instrument to the Western New York region. The facility has provided open access to users from the University at Buffalo (UB), our regional partners Roswell Park Cancer Inst. (RPCI) and Hauptman-Woodward Research Inst. (HWI), and occasional local college users. The current active user base is approximately 24 lab groups, the majority of which are NIH-funded. The facility also provides professional staff to train and assist new users, or perform collaborative work with less frequent users. Faculty associated with this facility and proposal also includes CD-related instruction in graduate-level courses, to provide graduate- and postdoctoral trainees with a sound basis of the theory and the potential applications of CD in their research projects.