Purchase of a MALDI-TOF Mass Spectrometer

该提案的目标是购买MALDI-TOF质谱仪，以加强韦恩州立大学在以下领域正在进行的研究计划：A）修饰的核酸结构（天然修饰的RNA、DNA-致癌物加合物、铂化DNA、具有非天然碱基修饰的DNA），B）蛋白质结构和相互作用（新的金属蛋白、磷酸化和后修饰的蛋白、DNA聚合酶和抗体），和C）糖肽化学（α-Gal表位模拟文库）。这些主题代表了化学和药理学系五个由NIH资助的实验室的研究领域。至少75%的仪器时间将用于这些项目。剩下的25%的仪器时间将用于韦恩州立大学的其他活跃研究领域，包括A）PDZ蛋白结构域和B）有机树枝状聚合物的研究。韦恩州立大学目前没有一个中央共享的MALDI-TOF质谱仪。申请人非常需要这种重要的分析工具，以便以简单、准确且需要很少材料的方式进行生物分子（RNA、DNA、碳水化合物和蛋白质）、聚合物和合成天然产物的常规表征。MALDI-TOF/MS的加入将大大提高我们以高通量分析这些分子的能力。由于韦恩州立大学从事大分子研究的团体越来越多，包括最近在生物有机和生物无机化学领域的几个雇员，我们的需求远远超过了目前LC/MS仪器的能力。添加MALDI-TOF将允许更优化地使用当前的LC/MS仪器，因此这两种仪器将具有互补作用。要求的MALDI-TOF仪器将存放在韦恩州立大学中央仪器设施（CIF）的化学部门。该机制有内部和外部资金支持，确保该工具得到适当维护，并以最有效的水平运作。CIF提供博士学位-在质谱技术方面，高级专家将发挥关键的咨询作用，而质谱和MALDI-TOF方面的几位内部专家将发挥关键的咨询作用。

The goal of this proposal is to purchase a MALDI-TOF mass spectrometer to enhance ongoing research programs at Wayne State University in the areas of A) modified nucleic-acid structure (naturally modified RNAs, DNA-carcinogen adducts, platinated DNAs, DNAs with non-natural base modifications), B) protein structure and interactions (novel metalloproteins, phosphorylated and post- translationally modified proteins, DNA polyrnerases, and antibodies), and C) glycopeptide chemistry (alpha-Gal epitope mimetic libraries). These topics represent the research areas of five established NIH- funded laboratories in the Departments of Chemistry and Pharmacology. At least 75% of the instrument time will be devoted to these projects. The remaining 25% of instrument time will be devoted to other active research areas at Wayne State, including the study of A) PDZ protein domains and B) organic dendrimers. A central, shared MALDI-TOF mass spectrometer is currently not available at Wayne State. This important analytical tool is very much needed by the applicants in order to carry out routine characterization of biomolecules (RNAs, DNAs, carbohydrates, and proteins), polymers, and synthetic natural products in a manner that is facile, accurate, and requires little material. The addition of MALDI-TOF/MS will greatly enhance our ability to analyze these molecules with high throughput. Due to the increasingly large number of groups at Wayne State performing studies on macromolecules, including several recent hires in the areas of bioorganic and bioinorganic chemistry, our demands have far exceeded the capabilities of the current LC/MS instrument. The addition of MALDI-TOF will allow for more optimal use of the current LC/MS instrument and the two instruments would therefore have complementary roles. The requested MALDI-TOF instrument will be housed in the Chemistry Department in the Central Instrument Facility (CIF) at Wayne State. The facility has both internal and external funding support, assuring that the instrument will be properly maintained and operated at the most efficient level. The CIF provides Ph.D.-level expertise in mass spectral techniques, and several in-house experts on mass spectrometry and MALDI-TOF will play key advisory roles.