Construction of a Step-Scanning Vibrational Circular Dichroism Instrument

9318233斯威尼这项提议要求仪器允许组装一台采用振动圆二向色性(VCD)的新光谱仪的原型；光学装置将包括一台基于傅里叶变换方法的步进扫描干涉仪。该光谱仪将是此类光谱仪中的第一台，能够将VCD测量的灵敏度提高2到3个数量级。这种仪器的一个独特功能是能够检测寿命在纳秒范围内的溶液结构--这些结构在核磁共振分析中通常是看不见的。这将使其适用于涉及生物大分子的广泛的结构问题。主要用户之一Max Diem博士在VCD方面拥有丰富的经验，几年前在NSF赠款基金的帮助下设计和制造了自己的仪器。该仪器目前正在化学系用于多肽和多核苷酸结构研究，但其灵敏度仅限于1千道尔顿范围内的分子。来自亨特和纽约大学的实验室描述了各种项目，包括研究溶液中蛋白质和核酸结构的基本方面，金属蛋白质的结构，蛋白质合成中起始复合体的各个方面，以及药物-DNA相互作用，以及金属络合化疗药物的设计。预计新仪器将吸引更多来自斯隆-凯特琳癌症研究所、洛克菲勒大学和纽约市其他机构的用户。

9318233 Sweeney This Proposal requests instrumentation to permit the assembly of a prototype of a new spectrometer, employing vibrational circular dichroism (VCD); the optics will incorporate a step-scanning interferometer, based on a Fourier transform methodology. The spectrometer will be the first of its kind and will be capable of increasing the sensitivity of VCD measurements by 2 to 3 orders of magnitude. A unique feature of such an instrument will be its ability to detect solution structures with lifetimes in the nanosecond range -- structures normally invisible in NMR analysis. This will make it applicable to a broad range of structure problems involving biological macromolecules. One of the major users, Dr. Max Diem, has extensive experience in VCD, having designed and built his own instrument with the help of NSF grant funds several years ago. This instrument is currently being used for polypeptide and polynucleotide structural studies in the Chemistry Department, but its sensitivity limits its use to molecules in the range of one kilo-Dalton. Various projects are described, from laboratories at Hunter and at New York University, which include investigations of basic aspects of protein and nucleic acid structures in solution, structures of metalloproteins, and facets of the initiation complex in protein synthesis, as well as drug-DNA interactions, and the design of metal-complexed chemotherapeutic agents. It is anticipated that the new instrument will attract additional users from the Sloan-Kettering Institute for Cancer Research, the Rockefeller University and other institutions in New York City.