Circular Dichroism Spectropolarimeter with fluorescence acquisition and temperatu

描述（申请人提供）：在由该提案的八名共同研究者进行的NIH支持的核心项目中，圆二色性（CD）光谱偏振法为蛋白质构象和解折叠的动态方面提供了一个独特的窗口，伴随肽-膜相互作用和插入的构象转变，免疫原性更低，更有效的治疗性蛋白质制剂的开发，以及发现难溶性抗癌药物的替代制剂。我们寻求获得一个国家的最先进的CD分光偏振仪，以支持和加强这些研究计划。这一工具将为分布在这一区域地理区域的三个大学校园之一的一个得到良好支持但服务不足的调查小组提供方便。仪器上的特定附件将使独特的实验方法成为可能，例如程序化重复，多个样品的同时分析，程序化热斜坡研究以探测大分子构象，采集与CD测量交错的荧光发射数据，以及包含用于变性/重折叠研究的自动滴定仪。这些能力将大大增强现有NIH支持的项目。该仪器将由药物科学仪器设施操作，该设施自1995年以来一直成功地运作，当时它将第一台共享光盘仪器带到了西纽约地区。该设施向布法罗大学（UB）、我们的区域合作伙伴罗斯威尔公园癌症研究所（RPCI）和豪普特曼-伍德沃德研究所（HWI）的用户以及偶尔的当地大学用户提供开放访问。目前活跃的用户群大约有24个实验室小组，其中大部分是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。与该设施和建议相关的学院还包括研究生课程中与CD相关的教学，为研究生和博士后学员提供理论的坚实基础以及CD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.