Action spectra of chiral secondary structure

doi:10.1126/science.abc1294

GSTDTAP > 气候变化

DOI	10.1126/science.abc1294
	Action spectra of chiral secondary structure
	Perdita Barran
	2020-06-26
发表期刊	Science
出版年	2020
英文摘要	Louis Pasteur has particular resonance in the midst of the coronavirus disease 2019 (COVID-19) pandemic, given his work on the germ theory of disease that led to the development of vaccines for rabies and anthrax. Some years before these better-known discoveries, Pasteur had already made a great contribution to science with his observation of molecular chirality in crystals ([ 1 ][1]). Chirality is a fundamental property of molecular asymmetry, which in turn dictates the secondary structure of proteins and gives rise to handedness in DNA helices. Some 170 years later, on page 1465 of this issue, Daly et al. ([ 2 ][2]) present a new method, mass-resolved electronic circular dichroism (CD) ion spectroscopy, that allows the chirality of secondary structures—in this case, isolated guanine-rich DNA quadruplexes—to be unambiguously defined. In the 1830s, the acceptance of the concept of chemical structure was some decades away, but developments in optics were revealing regularity in the ordering of crystalline materials at a submicrometer level. Light could be filtered through polarizing optics, such as Nicol prisms. Although not understood at the time, this process causes the oscillating electric field of the light to move in only one direction. Using a polarized light source, Jean-Baptiste Biot ([ 3 ][3]) observed that a saturated solution of tartaric acid would rotate the polarized light clockwise or anticlockwise, but he presented no explanation for this phenomenon. Some 20 years later, in 1848, Pasteur crystallized paratartaric acid, produced from overboiled wine, and noticed that it produced two types of crystals, one that looked like tartaric acid crystals and one that did not. He repeated Biot's experiment with a 50-50 mixture of these crystals and found that this solution would not rotate the polarized light. From these observations, Pasteur concluded that each crystal had an intrinsic property, and that the material in each crystal was the mirror image of the other, like a left and a right hand. Pasteur named this phenomenon chirality (from kheir , the Greek word for hand). It soon became evident that this is a property of fundamental importance to chemistry, where different substituents on tetravalent carbon create a chiral center. ![Figure][4] An exciting way to measure handedness Molecular handedness (chirality) is usually measured with circular dichroism, in which the direction of polarized light is rotated by absorption of light by molecules in solution. Daly et al. determined such spectra for individual molecules in the gas phase. GRAPHIC: V. ALTOUNIAN/ SCIENCE Naturally occurring biopolymers such as proteins and DNA are made of monomeric units with such chiral centers. When these repeat at regular intervals, they favor repeating noncovalent interactions that give rise to distinctive secondary structural motifs with characteristic optical signatures. Circular dichroism, the modern version of the experiments of Biot and Pasteur, measures the absorbance of polarized light and can verify, for example, that secondary structures of proteins are correctly folded. However, CD measures the aggregate effect of a mixture and can be insensitive to the presence of an enantiomer at lower concentrations, or to the particular form of the molecule that is causing the optical rotation. To address this limitation, Daly et al. built an experimental apparatus that can make precise measurements of chirality in biomolecules (see the figure). Unlike an optical absorption experiment in solution, the optical source (laser excitation) releases characteristic photoelectrons that lead to charge-reduced ions, so this method is an action spectroscopy. Electrospray ionization introduces guanine-rich DNA quadruplex molecules of different chirality into the vacuum chamber of a mass spectrometer. This transfer is performed carefully under conditions that aim to leave the solvated structure unperturbed. A few thousand molecular ions are trapped and irradiated with polarized laser light. The masses of the left- and right-handed forms of these DNA complexes are identical, so mass spectrometry alone cannot determine chirality. Further, unlike solution experiments where the concentration of molecules is high enough that the absorbance of light can be readily measured, the gas-phase DNA ions are dilute. Instead, Daly et al. use the mass spectrometer to measure the action of the polarized light on the DNA molecule. Facile release of a photoelectron upon irradiation gives a signal caused by the formation of the charge-reduced anion. The laser light pulses are polarized, so the efficiency of photoelectron removal depends on the helix handedness. By monitoring the intensity of the distinctive charge-reduced species as a function of the polarization, they are able to determine the chirality of the molecule. This type of experiment can isolate any given molecular complex because each analyte is unequivocally defined by its mass-to-charge ratio. Prior work by this group revealed coexisting structures formed by oligonucleotides in the presence of cations or organic molecules ([ 4 ][5]); this work was aimed at understanding the balance of forces that guide folding and self-assembly. Stoichiometry and quantitative measurements of nucleic acid complexes were readily made by combining mass and ion-mobility spectrometries, but this approach could not determine chirality or details of secondary structure. Mass-resolved electronic CD ion spectroscopy complements other structural mass spectrometry methods because it can provide secondary structure information in addition to molecular identity. Daly et al. also studied complexes of DNA with ammonium and potassium counterions and obtained a tantalizing glimpse of the effects of individual molecule solvation. The wavelength dependence of the action of polarized light followed the same trend as data obtained in solution, albeit with differences in magnitude, indicating that structures are preserved and that these gas-phase results are relevant to molecules in solution. They extended their measurement on human telomeric DNA sequences to determine enantiomeric ratios of mixtures of G-quadruplex topologies. Intriguingly, the difference in electron-detachment efficiency for the left-handed molecule and the right-handed molecule under a given circularly polarized light is equivalent to the slight enantiomeric excess in the products—up to 1% at some wavelengths—thereby demonstrating the high sensitivity as well as the potential of this new method. 1. [↵][6]1. L. Pasteur , C. R. Séances Acad. Sci. 26, 535 (1848). [OpenUrl][7] 2. [↵][8]1. S. Daly, 2. F. Rosu, 3. V. Gabelica , Science 368, 1465 (2020). [OpenUrl][9][Abstract/FREE Full Text][10] 3. [↵][11]1. J.-B. Biot , Mem. Acad. Sci. Inst. Fr. 15, 93 (1836). [OpenUrl][12] 4. [↵][13]1. M. Porrini et al ., ACS Cent. Sci. 3, 454 (2017). 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领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/278201
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Perdita Barran. Action spectra of chiral secondary structure[J]. Science,2020.
APA	Perdita Barran.(2020).Action spectra of chiral secondary structure.Science.
MLA	Perdita Barran."Action spectra of chiral secondary structure".Science (2020).