气相碎片化作为G-四重复形成的探测器
Nicole M Brundridge1, Jonathan Dickerhoff2, Danzhou Yang1,2
1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
Analytical chemistry
|September 29, 2023
概括
使用质谱学研究了气相中的G-四重复 (G4) DNA稳定性. 温和的激活条件揭示了G4结构在碎片化中的敏感性,将G4与非G4序列区分开来.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 质谱测量质量谱测量
背景情况:
- 在瘤基因促进体和端粒中,G-四重复 (G4) DNA 结构很普遍,呈现出有吸引力的抗癌标.
- G4的形成是由富含关氨酸的序列促进的,并由金属和连接体稳定.
- 了解G4的保存和稳定性对于治疗的发展至关重要.
研究的目的:
- 利用质谱学探索气相中的G-四重复二次结构的保存和稳定性.
- 为了研究G4结构在不同的碰撞诱导解离能量下对碎片化的敏感性.
- 根据它们的碎片化模式,区分G4形成和非G4形成的DNA序列.
主要方法:
- 使用线性四极离子陷确定了类似G4 (MycG4) 和非类似G4 (MycNonG4) 离子结构的碰撞诱导解离动力学.
- 分析的重点是高低离子激活能量的碎片化模式.
- 动力测量比较了与结合和无G4离子的碎片化速率.
主要成果:
- MycG4和MycNonG4的高能碎片化模式类似,表明对G4结构的敏感性较低.
- 在低能量下,碎片化模式显著不同,G4结构在气相中显示保存的折叠.
- 与结合的G4离子碎片化速度比它们的无对应物慢2-3倍,这是G4折叠的特殊现象.
结论:
- 在质谱学中,温和的激活条件使碎片化行为对G-quadruplex结构敏感.
- 这种方法可以揭示异构体结构的动态稳定性的差异,并确定涉及G4形成的序列区域.
- 这些发现支持质谱作为研究G4稳定性和结构的工具,这与抗癌药物开发有关.
相关概念视频
Mass Spectrometry: Molecular Fragmentation Overview
3.2K
The ionization of a molecule into a molecular ion inside the mass spectrometer causes instability in the molecule's structure due to the loss of an electron. This eventually leads to the fragmentation or breaking of some bonds in the molecule. The fragmentation occurs predominantly at specific bonds to yield relatively stable fragments.
One type of fragmentation pattern is the cleavage of a single bond in the molecular ion. The cleavage leads to a radical and a cation. The cleavage can...
One type of fragmentation pattern is the cleavage of a single bond in the molecular ion. The cleavage leads to a radical and a cation. The cleavage can...
3.2K
Mass Spectrometry: Carboxylic Acid, Ester, and Amide Fragmentation
1.4K
The fragmentation patterns observed for compounds such as carboxylic acids, esters, and amides in the mass spectra include ⍺-cleavage and McLafferty rearrangement. Fragmentation by ⍺-cleavage preferentially occurs at the carbon-carbon bond at the ⍺-position next to the carboxylic group to generate a neutral radical and a cation. Long chain compounds with hydrogen at their γ-carbon undergo McLafferty rearrangement to give a radical cation and a neutral alkene.
For example,...
For example,...
1.4K
¹H NMR: Complex Splitting
1.3K
A proton M that is coupled to a proton X results in doublet signals for M. However, NMR-active nuclei can be simultaneously coupled to more than one nonequivalent nucleus. When M is coupled to a second proton A, such as in styrene oxide, each peak in the doublet is split into another doublet.
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied...
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied...
1.3K
Maxam-Gilbert Sequencing
11.2K
In the same year as the discovery of the Sanger sequencing method, another group of scientists, Allan Maxam and Walter Gilbert, demonstrated their chemical-cleavage method for DNA sequencing. The Maxam-Gilbert method relies on using different chemicals that can cleave the DNA sequence at specific sites, the separation of resulting DNA fragments of variable size using electrophoresis, and deciphering the DNA sequence from the resulting gel bands.
Challenges of the Maxam-Gilbert Method
The...
Challenges of the Maxam-Gilbert Method
The...
11.2K
Mass Spectrometry: Branched Alkane Fragmentation
1.0K
This lesson delves into the mass spectrometry of branched alkane fragmentation. Branched alkanes possess secondary or tertiary carbon atoms, which generate relatively stable carbocations if the cleavage occurs at the branching point. The high stability of carbocations drives the instant fragmentation of branched alkanes. Accordingly, the branched alkane's molecular ion peak is very weak or invisible in the mass spectra, especially in comparison to a linear alkane.
1.0K
Mass Spectrometry: Alcohol Fragmentation
3.6K
Alcohols (R-OH) ionize to lose one non-bonded electron from the oxygen atom, forming molecular ions. Due to their tendency to fragment rapidly, the intensity of the molecular ion peak in the mass spectrum is weak or sometimes absent. The fragmentation patterns for alcohols occur in two ways, i.e. ⍺-cleavage and dehydration. During ⍺-cleavage, the bond at the ⍺-position adjacent to the hydroxyl group cleaves to give a resonance-stabilized cation and a radical. However,...
3.6K


