Purchase of a MALDI-TOF Mass Spectrometer

该提案的目标是购买MALDI-TOF质谱计，以加强韦恩州立大学正在进行的研究项目：a)修饰的核酸结构（自然修饰的rna， DNA致癌物质加合物，铂化DNA，非天然碱基修饰的DNA）， B)蛋白质结构和相互作用（新型金属蛋白，磷酸化和翻译后修饰的蛋白质，DNA聚合酶和抗体），C)糖肽化学（α - gal表位模拟文库）。这些课题代表了由美国国立卫生研究院资助的化学和药理学系的五个实验室的研究领域。至少75%的仪器时间将用于这些项目。其余25%的仪器时间将用于Wayne State的其他活跃研究领域，包括A) PDZ蛋白结构域和B)有机树状大分子的研究。韦恩州立大学目前没有中央共享的MALDI-TOF质谱仪。这个重要的分析工具是申请人非常需要的，以便以一种简单，准确和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高通量分析这些分子的能力。由于韦恩州立大学越来越多的团队在进行大分子的研究，包括最近在生物有机和生物无机化学领域的几个招聘，我们的需求远远超过了当前LC/MS仪器的能力。MALDI-TOF的加入将使当前LC/MS仪器的使用更加优化，因此这两种仪器将具有互补的作用。所要求的MALDI-TOF仪器将被安置在韦恩州立大学中央仪器设施（CIF）的化学系。该设施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方式运作。CIF在质谱技术方面提供博士级专业知识，并且几位质谱和MALDI-TOF方面的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.