MASS SPECTROMETRY OF ANTITUMOR AGENTS

本研究的目的是应用快原子技术 轰击质谱（FABMS）的问题，涉及的结构 说明合成和天然存在的抗肿瘤剂， 抗肿瘤剂的代谢物和抗肿瘤剂之间形成的复合物 试剂和寡脱氧核苷酸。 一种独特的方法来扩大 选择可用作FAB基质的溶剂， 可加热/可冷却的探针。 FABMS的应用也将是独一无二的 涉及完整线性和交联药物-寡核苷酸的分析 加合物 质谱结构-碎片化关系将 为那些以前没有研究过或研究过的化合物类开发， 只是有限的程度。 天然抗肿瘤药物的结构 临床上重要的抗癌药物的药剂和代谢物将被 根据高分辨率质量测量结果暂时指定， 亚稳态的研究和结构-断裂关系 在这些研究中发展起来的。 本建议书中所述的项目将与 与其他参与设计的医学和药物化学家一起， 抑制剂合成和配制。 利用大众 因此，光谱学在解决结构问题方面可能是 在开发新的抗肿瘤药物或 提高目前临床上使用的药物的临床疗效。 待测化合物类别的质谱分析，例如， 丝裂霉素C的类似物、链黑菌素、米托蒽醌通常 需要使用FAB。 电子碰撞（EI）和化学电离（CI） 也将用于天然产物和代谢产物的鉴定 问题研究 解吸化学电离（DCI）将作为 在米托蒽醌类似物的情况下，如果需要，可替代FAB。

The objective of this research is to apply the technique of fast atom bombardment mass spectrometry (FABMS) to problems involving the structure elucidation of synthetic and naturally occurring antitumor agents, metabolites of antitumor agents and complexes formed between antitumor agents and oligodeoxynucleotides. A unique approach to expanding the selection of solvents available for use as the FAB matrix will be the use of a heatable/coolable probe. Also unique will be the application of FABMS to the analysis of intact linear and cross-linked drug-oligonucleotide adducts. Mass spectral structure-fragmentation relationships will be developed for those compound classes not previously studied or studied to only a limited extent. The structure of naturally occurring antitumor agents and metabolites of clinically important anticancer drugs will be tentatively assigned on the basis of high resolution mass measurements, metastable on studies and the structure-fragmentation relationships developed in the course of these studies. The projects described in this proposal will be performed in collaboration with other medicinal and pharmaceutrical chemists involved in the design, synthesis and formulation of antineoplastic agents. The use of mass spectrometry in solving structural problems could, therefore, be of fundamental importance in development of new antitumoragents or in increasing the clinical efficacy of drugs currently being used clinically. Mass spectral analysis of the compound classes to be examined, e.g., analogs of mitomycin C, streptonigrin, mitoxantrone, will, in general require the use of FAB. Electron impact (EI) and chemical ionization (CI) will also be used in the natural product and metabolite identification studies. Desorption chimical ionization (DCI) will be examined as an alternative to FAB in the case of mitoxantrone analogs, if necessary.