An LC-TOF for Accurate Molecular Mass Determinations

描述（由申请人提供）：要求为具有电喷雾、纳米喷雾和大气压化学电离的高性能LC-TOF仪器提供资金。HPLC将与电喷雾和APCI连接使用。正交加速度TOF分析仪提供精确的质量测定（5 ppm，m/z 609），外部校准质量范围高达m/z 10，000 da。分辨率指定为6000。与TDC检波器相比，该检波器和ADC连续数字平均器提供了改进的峰值形状和更宽的动态范围。ADC的这些特征允许分析真实同位素分布，包括信号与样本大小的HID交换产物相关性，例如通过R=0.998的四个数量级。主要用户建议使用该仪器; .鉴定参与寡核苷酸的自加合物形成和靶向烷基化的关键亲核试剂，以确定这些过程的动力学;表征由疏水效应构建的非天然自组装体，例如自互补两亲物和自分选分子夹; .分析和定位氢/氘交换，以表征生物素阻遏物组装转录调控复合物中的关键中间体; .表征聚泛素链，合成和同位素标记的类似物，用于随后的NMR研究和动力学; .表征非天然的潘司他汀类似物、链黑菌素和nephritogenoside合成中的中间体。 该仪器将被安置在现有的部门中央仪器设施，在那里它将由工作人员质谱师诺埃尔惠特克先生管理，并由他和训练有素的用户操作。预计从事化学、生物化学和细胞生物学等广泛领域工作的科学家使用该仪器将有助于促进跨学科的讨论和合作。

DESCRIPTION (provided by applicant): Funding is requested for a high performance LC-TOF instrument with electrospray, nanospray and atmospheric pressure chemical ionization. An HPLC will be interfaced for use with electrospray and APCI. The orthogonal acceleration TOF analyzer provides accurate mass determinations (5ppm at m/z 609) with an externally calibrated mass range up to m/z 10,000 da. Resolution is specified as 6000. The detector, and ADC continuous digital averager, provides improved peak shapes and wider dynamic range, compared to TDC detectors. These features of the ADC allow analysis of true isotope distributions, including HID exchange product correlation of signal to sample size, e.g. through four orders of magnitude with an R=0.998. Major users propose to use the instrument to; . Identify key nucleophiles involved in self-adduct formation and target alkylation of oligonucleotides, to determine the kinetics of these processes; Characterize non-natural self assemblies constructed by hydrophobic effects, e.g. self complementary amphiphiles and self sorted molecular clips; . Analyze and localize hydrogen/deuterium exchange to characterize a key intermediate in the assembly transcriptional regulatory complex of the biotin repressor; . Characterize polyubiquitin chains, synthetic and isotope labeled analogs for subsequent NMR studies and dynamics; . Characterize intermediates in the synthesis of un-natural analogs of pancratistatin, streptonigrin and nephritogenoside. The instrument will be housed in the existing Departmental Central Instrumentation Facility, where it will be managed by the staff mass spectroscopist Mr. Noel Whittaker, and operated by him and trained users. It is anticipated that the use of the instrument by scientists working across a broad range of chemistry, biochemistry and cell biology will help stimulate cross-disciplinary discussions and collaboration.