國立臺灣師範大學博碩士論文全文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	黃詩珮 Huang, Shih-Pei
論文名稱：	以碰撞誘導解離串聯質譜法的邏輯程序應用於低聚半乳糖的結構鑑定 Logically Derived Collision-Induced Dissociation Sequence Tandem Mass Spectrometry on De Novo Structural Determination of Galactose Oligosaccharides
指導教授：	林震煌 Lin, Cheng-Huang 倪其焜 Ni, Chi-Kung
學位類別：	碩士 Master
系所名稱：	化學系 Department of Chemistry
論文出版年：	2018
畢業學年度：	106
語文別：	英文
論文頁數：	74
中文關鍵詞：	寡醣、結構、半乳糖、質譜、碰撞誘導解離
英文關鍵詞：	Oligosaccharides, Structure, Galactose, Mass Spectrometry (MS), Collision-Induced Dissociation (CID)
DOI URL：	http://doi.org/10.6345/THE.NTNU.DC.016.2018.B05
論文種類：	學術論文
相關次數：	點閱：162 下載：1
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

醣由數個單醣（Monosaccharides）組成，單醣與單醣間，以糖苷鍵（Glycosidic Bond）鍵結，形成高度複雜的結構。若想更進一步了解醣在這些生物系統中扮演的角色，就須要知道這些糖苷鍵如何鍵結。到目前為止，已經發展各種不同解醣結構的方法，但仍然沒有一個方法能快速且準確的解出每一個醣的結構。因此，本研究利用高效液相層析法（High-Performance Liquid Chromatography, HPLC）及質譜分析法（Mass Spectrometry）建立這個雙醣質譜的資料庫，並以醣解離機制的原理，建立解離順序，再藉由碰撞誘導解離（Collision-Induced Dissociation, CID）將寡醣分解成數個雙醣（Disaccharides）碎片，並將這些雙醣碎片的質譜（Mass Spectra）分別與我們建立的雙醣質譜的資料庫進行比對，快速的鑑定醣的結構。本研究使用幾個已知的寡醣作為例子，藉由此次提出的方法，解出這些寡醣的結構。

Carbohydrates are closely related to everyone life. It can be found in foods, blood, organisms, plants, bacteria, and so on. They are composed of different numbers of monosaccharides and present in various structures. Understanding these structures further assists the research of carbohydrate in biological systems. By now, many methods have been proposed to identify the structure of oligosaccharides. It is still challenging for these methods to resolve the structures in detail. In this study, a new rapid method that can identify the structure of oligosaccharides was demonstrated. This method was based on the comparison of disaccharide database with the spectra of disaccharides residues dissociated from oligosaccharide by collision-induced dissociation (CID). The disaccharides database was built using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MSn) and the spectra of disaccharide residues produced from CID of oligosaccharides were obtained by ESI-MSn. A logical procedure according to the dissociation mechanism was used to determine the sequence of tandem MS. This new method was applied to identify the oligosaccharides structures, including linkage positions, anomeric configurations, and branch locations. Here, several underived oligosaccharides with sodium ion adducts were used as examples to demonstrate this new method.

中文摘要 1
Abstract 2
Contents 4
List of Figures 7
List of Tables 11

1 Introduction 12
　1.1 Introduction of Carbohydrates 12
　1.2 Structure Identification Methods of Carbohydrates 15

2 Experiment Methods 16
　2.1 Mass Spectrometry (MS) 16
　　　2.1.1 Basic Concepts 16
　　　2.1.2 Ion Sources 17
　　　　　　2.1.2.1 Electro Ionization (EI) and Chemical Ionization (CI) 17
　　　　　　2.1.2.2 Matrix-Assisted Laser Desorption/Ionization (MALDI) 17
　　　　　　2.1.2.3 Electrospray Ionization (ESI) 18
　　　2.1.3 Analyzers 19
　　　　　　2.1.3.1 Quadrupole 19
　　　　　　2.1.3.2 Time-of-Flight (TOF) 20
　　　　　　2.1.3.3 Ion Traps 20
　　　2.1.4 Collision-Induced Dissociation (CID) 22
　2.2 High-Performance Liquid Chromatography (HPLC) 23
　2.3 Experimental Setup 24
　　　2.3.1 High-Performance Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (HPLC-ESI-MSn) 24
　　　2.3.2 Electrospray Ionization Tandem Mass Spectrometry (ESI-MSn) 25
　2.4 Materials 26

3 Logical Procedure to Determine the Structure of Oligosaccharides 27
　3.1 Mechanism of Dehydration 28
　3.2 Mechanism of Glycosidic Bond Cleavage 29
　3.3 Mechanism of Cross-Ring Dissociation 30
　3.4 Logical Procedure for Oligosaccharides 31

4 Results and Discussion 35
　4.1 Similarity Calculations 35
　4.2 Disaccharide Database 37
　4.3 Applications to Oligosaccharides 46
　　　4.3.1 α-Gal-(1→3)-β-Gal-(1→4)-Gal 46
　　　4.3.2 α-Gal-(1→3)-β-Gal-(1→4)-Glc 50
　　　4.3.3 β-Gal-(1→3)-β-Gal-(1→4)-Glc 54
　　　4.3.4 β-Gal-(1→4)-β-Gal-(1→4)-Glc 58
　　　4.3.5 α-Gal-(1→3)-β-Gal-(1→4)-α-Gal-(1→3)-Gal 61

5 Conclusion 67

6 Reference 68
                                

1. Bertozzi, C. R.; Kiessling, L. L. Chemical Glycobiology. Science 2001, 291(5512), 2357-2364.
2. Varki, A.; Cummings, R. D.; Esko, J. D.; Stanley, P.; Hart, G. W.; Aebi, M.; Darvill, A. G.; Kinoshita, T.; Packer, N. H.; Prestegard, J. H.; Schnaar, R. L.; Seeberger, P. H. Essentials of Glycobiology. Cold Spring Harbor Laboratory Press: New York, 2015-2017.
3. Zivkovic, A. M.; Barile, D. Bovine Milk as a Source of Functional Oligosaccharides for Improving Human Health. Adv. Nutr. 2011, 2(3), 284-289.
4. Domon, B.; Costello, C. E. A Systematic Nomenclature for Carbohydrate Fragmentations in FAB-MS/MS Spectra of Glycoconjugates. Glycoconj. J. 1988, 5(4), 397-409.
5. Duus, J.; Gotfredsen, C. H.; Bock, K. Carbohydrate Structural Determination by NMR Spectroscopy: Modern Methods and Limitations. Chem. Rev. 2000, 100(12), 4589-4614.
6. Cocinero, E. J.; Carcabal, P.; Vaden, T. D.; Simons, J. P.; Davis, B. G. Sensing the Anomeric Effect in a Solvent-Free Environment. Nature 2011, 469(7328), 76-79.
7. Cocinero, E. J.; Gamblin, D. P.; Davis, B. G.; Simons, J. P. The Building Blocks of Cellulose: The Intrinsic Conformational Structures of Cellobiose, Its Epimer, Lactose, and Their Singly Hydrated Complexes. J. Am. Chem. Soc. 2009, 131(31), 11117-11123.
8. Terol, A.; Paredes, E.; Maestre, S. E.; Prats, S.; Todoli, J. L. Rapid and Sensitive Determination of Carbohydrates in Foods Using High Temperature Liquid Chromatography with Evaporative Light Scattering Detection. J. Sep. Sci. 2012, 35(8), 929-936.
9. De Ruiter, G. A.; Schols, H. A.; Voragen, A. G. J.; Rombouts, F. M. Carbohydrate Analysis of Water-Soluble Uronic Acid-Containing Polysaccharides with High-Performance Anion-Exchange Chromatography Using Methanolysis Combined with TFA Hydrolysis Is Superior to Four Other Methods. Anal. Biochem. 1992, 207(1), 176-185.
10. Zaia, J. Mass Spectrometry of Oligosaccharides. Mass Spectrom. Rev. 2004, 23(3), 161-227.
11. Hillenkamp, F.; Karas, M.; Beavis, R. C.; Chait, B. T. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Biopolymers. Anal. Chem. 1991, 63(24), 1193A-1203A.
12. Fenn, J.; Mann, M.; Meng, C.; Wong, S.; Whitehouse, C. Electrospray Ionization for Mass Spectrometry of Large Biomolecules. Science 1989, 246(4926), 64-71.
13. Stephens, E.; Maslen, S. L.; Green, L. G.; Williams, D. H. Fragmentation Characteristics of Neutral N-Linked Glycans Using a MALDI-TOF/TOF Tandem Mass Spectrometer. Anal. Chem. 2004, 76(8), 2343-2354.
14. Kurimoto, A.; Daikoku, S.; Mutsuga, S.; Kanie, O. Analysis of Energy-Resolved Mass Spectra at MSn in a Pursuit to Characterize Structural Isomers of Oligosaccharides. Anal. Chem. 2006, 78(10), 3461-3466.
15. Vijayakrishnan, B.; Issaree, A.; Corilo, Y. E.; Ferreira, C. R.; Eberlin, M. N.; Peter, M. G. MSn of the Six Isomers of (Glcn)2(Glcnac)2 Aminoglucan Tetrasaccharides (Diacetylchitotetraoses): Rules of Fragmentation for the Sodiated Molecules and Application to Sequence Analysis of Hetero-Chitooligosaccharides. Carbohydr. Polym. 2011, 84(2), 713-726.
16. Nagy, G.; Pohl, N. L. Complete Hexose Isomer Identification with Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2015, 26(4), 677-685.
17. Li, D. T.; Her, G. R. Structural Analysis of Chromophore-Labeled Disaccharides and Oligosaccharides by Electrospray Ionization Mass Spectrometry and High-Performance Liquid Chromatography/Electrospray Ionization Mass Spectrometry. J. Mass Spectrom. 1998, 33(7), 644-652.
18. Cheng, H. L.; Her, G. R. Determination of Linkages of Linear and Branched Oligosaccharides Using Closed-Ring Chromophore Labeling and Negative Ion Trap Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2002, 13(11), 1322-1330.
19. Harvey, D. J. Fragmentation of Negative Ions from Carbohydrates: Part 1. Use of Nitrate and Other Anionic Adducts for the Production of Negative Ion Electrospray Spectra from N-Linked Carbohydrates. J. Am. Soc. Mass Spectrom. 2005, 16(5), 622-630.
20. Harvey, D. J. Fragmentation of Negative Ions from Carbohydrates: Part 2. Fragmentation of High-Mannose N-Linked Glycans. J. Am. Soc. Mass Spectrom. 2005, 16(5), 631-646.
21. Guan, B.; Cole, R. B. MALDI Linear-Field Reflectron TOF Post-Source Decay Analysis of Underivatized Oligosaccharides: Determination of Glycosidic Linkages and Anomeric Configurations Using Anion Attachment. J. Am. Soc. Mass Spectrom. 2008, 19(8), 1119-1131.
22. Harvey, D. J.; Jaeken, J.; Butler, M.; Armitage, A. J.; Rudd, P. M.; Dwek, R. A. Fragmentation of Negative Ions from N-Linked Carbohydrates, Part 4. Fragmentation of Complex Glycans Lacking Substitution on the 6-Antenna. J. Mass Spectrom. 2010, 45(5), 528-535.
23. Konda, C.; Bendiak, B.; Xia, Y. Linkage Determination of Linear Oligosaccharides by MSn (n > 2) Collision-Induced Dissociation of Z1 Ions in the Negative Ion Mode. J. Am. Soc. Mass Spectrom. 2014, 25(2), 248-257.
24. Viseux, N.; de Hoffmann, E.; Domon, B. Structural Assignment of Permethylated Oligosaccharide Subunits Using Sequential Tandem Mass Spectrometry. Anal. Chem. 1998, 70(23), 4951-4959.
25. van der Kerk, S. M.; Blok-tip, L.; van der Kerk-van Hoof, A.; Heerma, W.; Haverkamp, J. Differences in Fragmentation Behaviour between a- and b-Linked Derivatized Xylobiosides: Explanation in Terms of Sigma Conjugation. Int. J. Mass Spectrom. Ion Proc. 1994, 134(1), 41-54.
26. Xue, J.; Song, L.; Khaja, S. D.; Locke, R. D.; West, C. M.; Laine, R. A.; Matta, K. L. Determination of Linkage Position and Anomeric Configuration in Hex-Fuc Disaccharides Using Electrospray Ionization Tandem Mass Spectrometry. Rapid Commun. Mass Spectrom. 2004, 18(17), 1947-1955.
27. Mendonca, S.; Cole, R. B.; Zhu, J.; Cai, Y.; French, A. D.; Johnson, G. P.; Laine, R. A. Incremented Alkyl Derivatives Enhance Collision Induced Glycosidic Bond Cleavage in Mass Spectrometry of Disaccharides. J. Am. Soc. Mass Spectrom. 2003, 14(1), 63-78.
28. Ashline, D.; Singh, S.; Hanneman, A.; Reinhold, V. Congruent Strategies for Carbohydrate Sequencing. 1. Mining Structural Details by MSn. Anal. Chem. 2005, 77(19), 6250-6262.
29. Zhang, H.; Singh, S.; Reinhold, V. N. Congruent Strategies for Carbohydrate Sequencing. 2. FragLib: An MSn Spectral Library. Anal. Chem. 2005, 77(19), 6263-6270.
30. Park, Y.; Lebrilla, C. B. Application of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry to Oligosaccharides. Mass Spectrom. Rev. 2005, 24(2), 232-264.
31. Lattova, E.; Snovida, S.; Perreault, H.; Krokhin, O. Influence of the Labeling Group on Ionization and Fragmentation of Carbohydrates in Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2005, 16(5), 683-696.
32. Kailemia, M. J.; Ruhaak, L. R.; Lebrilla, C. B.; Amster, I. J. Oligosaccharide Analysis by Mass Spectrometry: A Review of Recent Developments. Anal. Chem. 2014, 86(1), 196-212.
33. Carlesso, V.; Fournier, F.; Tabet, J. C. Stereochemical Differentiation of Four Monosaccharides Using Transition Metal Complexes by Electrospray Ionization/Ion-Trap Mass Spectrometry. Eur. J. Mass Spectrom. 2017, 6(5), 421-428.
34. Dwek, R. A.; Edge, C. J.; Harvey, D. J.; Wormald, M. R.; Parekh, R. B. Analysis of Glycoprotein-Associated Oligosaccharides. Annu. Rev. Biochem. 1993, 62, 65-100.
35. Hoffmann, E. d.; Stroobant, V. Mass Spectrometry: Principles and Applications. John Wiley & Sons: USA, 2007.
36. 台灣質譜學會質譜分析技術：原理與應用. 全華圖書: 台灣, 2016.
37. Schwartz, J. C.; Senko, M. W.; Syka, J. E. P. A Two-Dimensional Quadrupole Ion Trap Mass Spectrometer. J. Am. Soc. Mass Spectrom. 2002, 13(6), 659-669.
38. Snyder, L. R.; Kirkland, J. J.; Dolan, J. W. Introduction to Modern Liquid Chromatography. John Wiley & Sons: 2010.
39. Tsai, S. T.; Chen, J. L.; Ni, C. K. Does Low-Energy Collision-Induced Dissociation of Lithiated and Sodiated Carbohydrates Always Occur at Anomeric Carbon of the Reducing End? Rapid Commun. Mass Spectrom. 2017, 31(21), 1835-1844.
40. Chen, J. L.; Nguan, H. S.; Hsu, P. J.; Tsai, S. T.; Liew, C. Y.; Kuo, J. L.; Hu, W. P.; Ni, C. K. Collision-Induced Dissociation of Sodiated Glucose and Identification of Anomeric Configuration. Phys. Chem. Chem. Phys. 2017, 19(23), 15454-15462.
41. Wan, K. X.; Vidavsky, I.; Gross, M. L. Comparing Similar Spectra: From Similarity Index to Spectral Contrast Angle. J. Am. Soc. Mass Spectrom. 2002, 13(1), 85-88.
42. Zhang, Z. Prediction of Low-Energy Collision-Induced Dissociation Spectra of Peptides. Anal. Chem. 2004, 76(14), 3908-3922.
43. Pigman, W.; Isbell, H. S. Mutarotation of Sugars in Solution: Part I. History, Basic Kinetics, and Composition of Sugar Solutions. Adv. Carbohydr. Chem. 1968, 23, 11-57.
44. Isbell, H. S.; Pigman, W. Mutarotation of Sugars in Solution: Part II: Catalytic Processes, Isotope Effects, Reaction Mechanisms, and Biochemical Aspects. Adv. Carbohydr. Chem. Biochem. 1969, 24, 13-65.

簡易檢索 / 詳目顯示

相關論文