Fast atom bombardment and tandem mass spectrometry of covalently modified nucleosides and nucleotides: adducts of pyrrolizidine alkaloid metabolites.
Fast atom bombardment and tandem mass spectrometry of covalently modified nucleosides and nucleotides: adducts of pyrrolizidine alkaloid metabolites.
复制标题
共价修饰核苷和核苷酸的快原子轰击和串联质谱：吡咯里西啶生物碱代谢物的加合物。
DOI：
10.1021/ac00125a037
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发表时间：
1986
影响因子：
7.4
通讯作者：
Deinzer,ML
中科院分区：
文献类型：
--
作者：
Tomer,KB;Gross,ML;Deinzer,ML
核苷酸的“H）”通过失去糖或生物碱并通过形成作为B”的核酸碱基而分解。含碱吨的丰度与已知的碱的稳定性有关。（+ H）+的分解导致生物碱作为亲电试剂的释放。质子化的核酸碱基（BH 2+）和化学修饰的碱基也形成，并且它们的丰度与碱基的质子亲和力相关。（+ K）+离子与（+ H）+离子的分解方式不同，主要产生10 ns的碱和钾离子。K+似乎主要与碱基或核苷部分相关，表明这些结构单元具有高钾离子亲和力。另一方面，质子与碱基和/或修饰的碱基更紧密地结合。裂解反应提供了与共价键合的生物碱分子量以及碱基、糖和生物碱修饰的性质和位点有关的信息，从各种遗传生物聚合物中检测和结构鉴定共价修饰的核苷和核苷酸在现代研究领域，特别是生物化学和肿瘤学中具有重要意义。化学家面临的一个挑战是开发出适用于高极性、热敏性材料的信息丰富的方法，并可应用于从生命系统中分离出的少量（微克或更少）材料。快原子轰击（FAB）（I，2）的出现为质谱学家提供了这样一种技术。FAB在分析各种非衍生化核苷、核苷酸、修饰核苷和核苷酸中的成功应用最近已被综述（3-7）。在FAB/MS分析的应用中存在几个潜在的缺点。一个是通常很少有碎片信息可用于结构确定。化学基质的使用可能会造成困难，因为低丰度碎片离子可能会被基质产生的化学噪音所掩盖。许多生物化学感兴趣的化合物以混合物形式存在，当碎片离子
H)" of the nucleotides decompose by losing either the sugar or the alkaloid and by forming the nucleic acid base as B". Theabundances of the base-containing tons correlate with the known stabilities of the bases. Decompo-sition of the (+ H)+ leads to liberation of the alkaloid as an electrophile. The protonated nucleic acid base (BH2+) and the chemically modified base are also formed, and their abundances correlate with the proton affinities of the bases.(+ K)+ ions decompose differently than the (+ H)+ to give principally 10ns containing the base moiety and potas-sium. K+ appears to be principally affiliated with the base or nucleoside moieties, Indicating that these structural units have high potassium Ion affinities. The proton, on the other hand, Is more closely associated with the base and/or the modified base. The fragmentation reactions provide information rela-ting to the molecular weight of the covalently bonded alkaloid and to the nature and sites of modification of the base, sugar, and alkaloid.The detection and structure elucidation of covalently modified nucleosides and nucleotides from variousgenetic biopolymers are important in a variety of modern research areas, particularly biochemistry and oncology. One challenge to the chemist is to develop suitable information-rich methods that are applicable to highly polar, thermally sensitive ma-terials and that can be applied to small (microgram or less) quantities isolated from living systems. The advent of fast atom bombardment (FAB)(I, 2) has provided the mass spectrometrist with such a technique. The successful application Of FAB to the analysis of a variety of nonderivatized nucleosides, nucleotides, and modified nu-cleosides and nucleotides has been reviewedrecently (3-7). There are several potential drawbacks in the application of FAB/MS analyses. One is that there is often little frag-mentation information which could be used for structure determination. The use of a chemical matrix can pose dif-ficulties in that low abundance fragment ions can be obscured by the chemical noise due to the matrix. As many of the compounds of biochemical interest exist as mixtures, assign-ment of parent-daughter relationships, when fragment ions