在NMR代谢分析中检测可交换的质子,使用人工智能设计的无脉冲辐射水进行代谢分析
Manu Veliparambil Subrahmanian1, Ivan Vuckovic2, Slobodan Macura3
1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Analytical chemistry
|February 5, 2025
概括
新的1D质子NMR技术消除了水信号,保持可交换的质子强度,以准确量化生物流体中的代谢物. 这提高了代谢障碍的诊断潜力.
科学领域:
- 核磁共振 (NMR) 光谱学 核磁共振 (NMR) 光谱学
- 代谢学 代谢学 代谢学
- 生物化学 生化学
背景情况:
- 质子NMR (1H NMR) 光谱对于生物流体中的代谢物分析至关重要,有助于疾病诊断.
- 目前的1H NMR方法使用溶剂抑制,这损害了用可交换质子对分析物的量化.
- 准确量化代谢物,特别是那些具有可交换质子的代谢物,在生物样本中仍然是一个挑战.
研究的目的:
- 开发新的1H NMR技术,以精确量化生物流体中的代谢物.
- 为了克服影响可交换质子信号的现有溶剂抑制方法的局限性.
- 提高NMR光谱在代谢学中的诊断效用.
主要方法:
- 使用GENETICS-AI.开发新的无水辐射 (WADE) 脉冲.
- 为代谢应用优化1D 1H NOESY序列.
- 对人类尿液,脏组织提取物和血样本应用新技术.
主要成果:
- 韦德技术成功地消除了水信号,同时保持可交换的质子强度.
- 在各种生物样本中实现了常见代谢物的精确量化.
- 证明了尿素的直接和准确量化,这在标准NMR中通常是困难的.
结论:
- 新的WADE脉冲和优化的1D 1H NOESY序列为代谢物量化提供了更高的准确性和可靠性.
- 这些进展有望显著提高NMR在生物流体代谢研究中的应用.
- 开发的技术有望为更精确的代谢障碍和其他疾病的诊断.
相关概念视频
01:12Double Resonance Techniques: Overview
185
Double resonance techniques in Nuclear Magnetic Resonance (NMR) spectroscopy involve the simultaneous application of two different frequencies or radiofrequency pulses to manipulate and observe two distinct nuclear spins. One important application of double resonance is spin decoupling, which selectively suppresses coupling with one type of nucleus while observing the NMR signal from another nucleus, simplifying the spectrum and enhancing resolution.
Spin decoupling is usually achieved by...
Spin decoupling is usually achieved by...
185
01:15Insensitive Nuclei Enhanced by Polarization Transfer (INEPT)
222
Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) is an advanced Nuclear Magnetic Resonance (NMR) technique specifically designed to detect and enhance the signals of low-abundance nuclei, such as carbon-13 and nitrogen-15, in small molecules. The fundamental principle behind INEPT is the transfer of polarization from a more abundant and highly polarizable nucleus, typically hydrogen-1, to the low-abundance nucleus of interest. This process effectively boosts the NMR signal of the...
222
01:07Proton (¹H) NMR: Chemical Shift
1.5K
Organic molecules primarily contain carbon and hydrogen atoms. While all the hydrogen isotopes are NMR-active, protium or hydrogen-1 is the most abundant. It has a significant energy separation between its nuclear spin states due to its large gyromagnetic ratio. As per Boltzmann's distribution, an increase in the energy separation implies a greater excess population of nuclei available for excitation, resulting in a strong NMR absorption signal.
Absorption signals of all the protium nuclei...
Absorption signals of all the protium nuclei...
1.5K
00:48¹H NMR of Labile Protons: Deuterium (²H) Substitution
873
This lesson illustrates the role of deuterium substitution in simplifying the NMR spectrum of compounds comprising labile protons. One method employed is the use of deuterium. Amongst the three isotopes of hydrogen, deuterium (2H) has a nucleus composed of one proton and one neutron. When the D2O solvent is added to a pure dry ethanol solution, its labile proton is substituted with deuterium.
873
01:17Chemical Shift: Internal References and Solvent Effects
591
In an NMR sample, precise measurement of the absolute absorption frequencies of nuclei is difficult. A standard internal reference compound is added, and the frequency difference between the reference signal and sample signals is measured.
The internal reference compound generally used in NMR spectroscopy is tetramethylsilane (TMS). TMS is preferred because it is chemically inert, soluble in NMR solvents, and easily removable. Also, the highly shielded methyl protons in TMS yield an intense...
The internal reference compound generally used in NMR spectroscopy is tetramethylsilane (TMS). TMS is preferred because it is chemically inert, soluble in NMR solvents, and easily removable. Also, the highly shielded methyl protons in TMS yield an intense...
591
01:20¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)
1.0K
When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
1.0K