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MASS SPECTROMETRY OF ANTITUMOR AGENTS

抗肿瘤剂的质谱分析

基本信息

批准号：
3183415
负责人：
KARL H SCHRAM
金额：
$ 10.86万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-03-01 至 1989-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3183415
关键词：
antineoplastics chemical addition chemical structure crosslink drug design /synthesis /production drug metabolism gas chromatography mass spectrometry ionization mass spectrometry mitomycin C mitoxantrone oligonucleotides

项目摘要

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.

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。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deuterium-labeled 3-nitrobenzyl alcohol as a matrix for fast atom bombardment mass spectrometry.

氘标记的 3-硝基苯甲醇作为快原子轰击质谱分析的基质。

DOI：
10.1002/bms.1200181209
发表时间：
1989
期刊：
Biomedical & environmental mass spectrometry
影响因子：
0
作者：
Reddy,AM;Mykytyn,VV;Schram,KH
通讯作者：
Schram,KH

Low nanogram detection of nucleotides using fast atom bombardment-mass spectrometry.

使用快原子轰击质谱法检测低纳克核苷酸。

DOI：
10.1016/0003-2697(89)90363-1
发表时间：
1989
期刊：
Analytical biochemistry
影响因子：
2.9
作者：
Weng,QM;Hammargren,WM;Slowikowski,D;Schram,KH;Borysko,KZ;Wotring,LL;Townsend,LB
通讯作者：
Townsend,LB

Mass spectrometry of nucleic acid components.

核酸成分的质谱分析。