学位论文详细信息
Characterization of Nucleic Acid Non-Covalent Interactions by FourierTransform Ion Cyclotron Resonance Tandem Mass Spectrometry and Gas-PhaseHydrogen/Deuterium Exchange.
Nucleic Acids;Non-covalent Interaction;Mass Spectrometry;Hydrogen/Deuterium Exchange;ESI;Chemistry;Science;Chemistry
Mo, JingjieWalter, Nils G. ;
University of Michigan
关键词: Nucleic Acids;    Non-covalent Interaction;    Mass Spectrometry;    Hydrogen/Deuterium Exchange;    ESI;    Chemistry;    Science;    Chemistry;   
Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/60742/jingjie_1.pdf?sequence=1&isAllowed=y
瑞士|英语
来源: The Illinois Digital Environment for Access to Learning and Scholarship
PDF
【 摘 要 】
One of the long-term goals of biological chemistry is to understand the relationship between the 3-dimensional structures of biomolecules and their biological functions.Nucleic acids play important roles in a variety of fundamental biological processes and understanding of their structures has a profound impact on the progress of biological chemistry research.Common biophysical methods used to probe biomolecular higher order structures include X-ray crystallography, nuclear magnetic resonance spectroscopy, fluorescence, circular dichroism, calorimetry, infrared spectroscopy, Raman spectroscopy, and electron spin resonance spectroscopy.Mass spectrometry (MS) has a major advantage over these methods due to its capability of identifying and determining the abundances of different complexes from direct observation because the mass of everymolecule serves as the intrinsic detection ;;label”.The utility of electrospray ionization (ESI) in MS to characterize non-covalent interactions of nearly every type of biomolecule has been described in numerous publications.In this thesis work, based on the ;;soft” characteristic of ESI, non-covalent interactions involved in higher order structures of nucleic acids as well as their complexes with small molecules were analyzed.Two strategies have been developed: first, a combination of infrared multiphoton dissociation and electron detachment dissociation and, second, gas-phase hydrogen/deuterium exchange (HDX) with MS detection.With the first strategy, different cleavage patterns were observed for three isomeric DNA 15-mers, indicating that this approach allows probing of higher order structures of nucleic acids.However, the cleavage efficiency is low due to the intrinsic instrument configuration.The second strategy was applied to compare a series of nucleic acid hairpins and was shown to be able to correlate their solution-phase stabilities with their gas-phase HDX rates.This method was also used to compare the binding affinities of A-site RNAs with different aminoglycoside antibiotics and the results were found to be similar to those in previous experiments.Furthermore, we propose a relay mechanism for oligonucleotide gas-phase HDX in both positive and negative ion mode, and show that the HDX rates of nucleic acids are dependent on the gas-phase basicity (positive ion mode) and acidity (negative ion mode) of the nucleobases as well as their structural flexibility.
【 预 览 】
附件列表
Files Size Format View
Characterization of Nucleic Acid Non-Covalent Interactions by FourierTransform Ion Cyclotron Resonance Tandem Mass Spectrometry and Gas-PhaseHydrogen/Deuterium Exchange. 1547KB PDF download
  文献评价指标  
  下载次数:16次 浏览次数:46次