MASS SPECTROMETRY OF ANTITUMOR AGENTS

抗肿瘤剂的质谱分析

• 批准号: 3183412
• 负责人: KARL H SCHRAM
• 金额: $ 14.04万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-03-01 至 1989-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183412
• 关键词: chemical addition; chemical structure; crosslink; drug design /synthesis /production; drug metabolism; gas chromatography mass spectrometry; ionization; mass spectrometry; mitomycin C; mitoxantrone; oligonucleotides

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.

这项研究的目的是应用快原子技术 轰击质谱学(FABMS)对涉及结构的问题 阐明合成和自然产生的抗肿瘤药物， 抗肿瘤药物的代谢物和抗肿瘤药物之间形成的络合物 药物和寡聚脱氧核苷酸。一个独特的方法来扩展 选择可用作FAB基质的溶剂将被使用 可加热/可冷却的探测器。FABMS的应用也将是独一无二的 完整线性和交联型药物寡核苷酸的分析 加合物。质谱学结构-裂解关系将是 为那些以前没有学习过或研究过的化合物类开发的 只有有限的范围。天然抗癌药物的结构 临床重要抗癌药物的药物和代谢物将 在高分辨率质量测量的基础上暂定， 亚稳态研究与结构-碎裂关系 在这些研究过程中发展起来的。 本建议书中描述的项目将在合作中执行 与参与设计的其他药物和药物中和化学家一起， 抗肿瘤药物的合成和配方。质量的使用 因此，光谱分析在解决结构问题方面可能是 在开发新的抗肿瘤药物或在 提高目前临床上使用的药物的临床疗效。 要检查的化合物类的质谱分析，例如， 丝裂霉素C、链球菌素、米托蒽醌的类似物，一般会 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物的鉴定 学习。解吸嵌合电离(DCI)将作为一种 如有必要，在米托蒽醌类似物的情况下替代FAB。