Liquid Chromatograph-Tandem Mass Spectrometer

请求提供资金，用于购置一台LC-MS-MS(LC-MS-MS)。主要用户来自化学系(3个)、生物化学系(2个)和生物系(2个)，代表了NIH资助的9个项目。没有得到NIH资助的少数用户来自化学(5)、生物学(1)、生物化学(2)和昆虫学(2)。在这些小项目中，有两个拨款提案正在等待美国国立卫生研究院的批准，很可能成为主要用户。LC-MS-MS是现代化学生物学的需要，是生物医学研究中的一个新兴领域。具有集成毛细管LC的三重四极杆MS-MS满足了建议使用该仪器的广泛项目的要求，从天然产物分离、代谢研究中的定量和小分子的组合化学到大分子领域的多肽和磷酸蛋白质的测序。这种仪器将具有弗吉尼亚理工大学的三重四极MS-MS的独特能力。Castagnoli教授将发现并表征神经保护和神经毒性药物。Etzkorn教授将设计和合成细胞周期酶抑制剂，作为潜在的抗癌药物。金斯顿教授将阐明天然产物的结构，设计和合成紫杉醇的衍生物，并研究紫杉醇与微管和微管结合的机制。波帕姆教授将对细菌细胞壁合成酶进行表征，并分析细胞壁结构的变化。Carlier教授将设计和合成GABA(A)受体的双价和多价探针，并将使用乙酰胆碱酯酶催化非天然化学反应。泰勒教授将展示超临界流体色谱学是类药物物质的质谱学鉴定/定量的可行界面。怀特教授将在古生代建立辅酶生物合成中间体。该仪器将安置在化学系的一个共享仪器实验室内，作为用户可进入的、操作员维护的设施运行。私人情报员Felicia Etzkorn与分析服务主任Geno Iannacone一起负责LC-MS-MS的购买、科学和行政监督。该仪器的用户培训、操作、维护和维修将由现任质谱学家Anne Campbell女士负责。

Funding is requested for the acquisition of a liquid chromatography- tandem mass spectrometer (LC-MS-MS). Major users are from the departments of Chemistry (3), Biochemistry (2), and Biology (2), representing 9 NIH-funded projects. Minor users not funded by the NIH are from Chemistry (5), Biology (1) Biochemistry (2), and Entomology (2). Of the minor projects, two grant proposals are pending with the NIH and are likely to become major users. The LC-MS-MS is required for modern chemical biology, a rising field in biomedical research. A triple quadrupole MS-MS with an integrated capillary LC fulfills the requirements for the broad range of projects proposed to use the instrument, from natural product isolation, quantitation in metabolism studies and combinatorial chemistry for small molecules to sequencing of peptides and phosphoproteins in the macromolecular area. This instrument would have the unique capabilities of a triple quadrupole MS-MS at Virginia Tech. Prof. Castagnoli will discover and characterize neuroprotective and neurotoxic agents. Prof. Etzkorn will design and synthesize inhibitors of cell-cycle enzymes as potential anti- cancer agents. Prof. Kingston will elucidate the structures of natural products, design and synthesize derivatives of paclitaxel and study the mechanism of paclitaxel binding to tubulin and microtubules. Prof. Popham will characterize bacterial cell wall synthetic enzymes and analyze changes in wall structure. Prof. Carlier will design and synthesize bi- and multivalent probes of the GABA(A) receptor, and will use acetylcholinesterase to catalyze non-native chemical reactions. Prof. Taylor will demonstrate that supercritical fluid chromatography is a viable interface for mass spectral identification/quantification of drug- like materials. Prof. White will establish coenzyme biosynthetic intermediates in the Archaea. The instrument will be housed in a shared instrumentation laboratory located in the Chemistry Department and operated as a user-accessible, operator-maintained facility. The P.I., Felicia Etzkorn, in conjunction with Geno Iannaccone, Director of Analytical Services, is responsible for purchase, scientific and administrative oversight of the LC-MS-MS. User training, operation, maintenance and repair of the instrument will be the responsibility of the current mass spectrometrist, Ms. Anne Campbell.