請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76613完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 邱繼輝 | |
| dc.contributor.author | Cheng-Te Hsiao | en |
| dc.contributor.author | 蕭正得 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:33:53Z | - |
| dc.date.available | 2021-07-10T21:33:53Z | - |
| dc.date.copyright | 2017-02-22 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-02-05 | |
| dc.identifier.citation | References
Alley, W.R., Jr., Madera, M., Mechref, Y., and Novotny, M.V. (2010). Chip-based reversed-phase liquid chromatography-mass spectrometry of permethylated N-linked glycans: a potential methodology for cancer-biomarker discovery. Anal Chem 82, 5095-5106. Amado, M., Carneiro, F., Seixas, M., Clausen, H., and Sobrinho-Simoes, M. (1998). Dimeric sialyl-Le(x) expression in gastric carcinoma correlates with venous invasion and poor outcome. Gastroenterology 114, 462-470. Apte, A., and Meitei, N.S. (2010). Bioinformatics in glycomics: glycan characterization with mass spectrometric data using SimGlycan. Methods Mol Biol 600, 269-281. Aspinall, G.O., and Monteiro, M.A. (1996). Lipopolysaccharides of Helicobacter pylori strains P466 and MO19: structures of the O antigen and core oligosaccharide regions. Biochemistry 35, 2498-2504. Björndal, H., Hellerqvist, C.G., Lindberg, B., and Svensson, S. (1970). Gas-Liquid Chromatography and Mass Spectrometry in Methylation Analysis of Polysaccharides. Angewandte Chemie International Edition in English 9, 610-619. Campbell, M.P., Ranzinger, R., Lutteke, T., Mariethoz, J., Hayes, C.A., Zhang, J., Akune, Y., Aoki-Kinoshita, K.F., Damerell, D., Carta, G., et al. (2014). Toolboxes for a standardised and systematic study of glycans. BMC Bioinformatics 15 Suppl 1, S9. Ceroni, A., Maass, K., Geyer, H., Geyer, R., Dell, A., and Haslam, S.M. (2008). GlycoWorkbench: a tool for the computer-assisted annotation of mass spectra of glycans. J Proteome Res 7, 1650-1659. Cheng, C.W., Chou, C.C., Hsieh, H.W., Tu, Z., Lin, C.H., Nycholat, C., Fukuda, M., and Khoo, K.H. (2015a). Efficient Mapping of Sulfated Glycotopes by Negative Ion Mode nanoLC-MS/MS-Based Sulfoglycomic Analysis of Permethylated Glycans. Anal Chem 87, 6380-6388. Cheng, P.F., Snovida, S., Ho, M.Y., Cheng, C.W., Wu, A.M., and Khoo, K.H. (2013). Increasing the depth of mass spectrometry-based glycomic coverage by additional dimensions of sulfoglycomics and target analysis of permethylated glycans. Anal Bioanal Chem 405, 6683-6695. Cheng, T.C., Tu, S.H., Chen, L.C., Chen, M.Y., Chen, W.Y., Lin, Y.K., Ho, C.T., Lin, S.Y., Wu, C.H., and Ho, Y.S. (2015b). Down-regulation of alpha-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface. Oncotarget 6, 21283-21300. Comelli, E.M., Sutton-Smith, M., Yan, Q., Amado, M., Panico, M., Gilmartin, T., Whisenant, T., Lanigan, C.M., Head, S.R., Goldberg, D., et al. (2006). Activation of murine CD4+ and CD8+ T lymphocytes leads to dramatic remodeling of N-linked glycans. J Immunol 177, 2431-2440. Cummings, R.D., and Nyame, A.K. (1996). Glycobiology of schistosomiasis. FASEB J 10, 838-848. Damerell, D., Ceroni, A., Maass, K., Ranzinger, R., Dell, A., and Haslam, S.M. (2012). The GlycanBuilder and GlycoWorkbench glycoinformatics tools: updates and new developments. Biol Chem 393, 1357-1362. Damerell, D., Ceroni, A., Maass, K., Ranzinger, R., Dell, A., and Haslam, S.M. (2015). Annotation of glycomics MS and MS/MS spectra using the GlycoWorkbench software tool. Methods Mol Biol 1273, 3-15. David, L., Nesland, J.M., Clausen, H., Carneiro, F., and Sobrinho-Simoes, M. (1992). Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn and T) in gastric mucosa, carcinomas and metastases. APMIS Suppl 27, 162-172. Dell, A. (1987). F.A.B.-mass spectrometry of carbohydrates. Adv Carbohydr Chem Biochem 45, 19-72. Dell, A., and Ballou, C.E. (1983). Fast-atom-bombardment, negative-ion mass spectrometry of the mycobacterial O-methyl-D-glucose polysaccharide and lipopolysaccharides. Carbohydr Res 120, 95-111. Desantos-Garcia, J.L., Khalil, S.I., Hussein, A., Hu, Y., and Mechref, Y. (2011). Enhanced sensitivity of LC-MS analysis of permethylated N-glycans through online purification. Electrophoresis 32, 3516-3525. Domon, B., and Costello, C.E. (1988). A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconjugate Journal 5, 397-409. Ellgaard, L., and Helenius, A. (2003). Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4, 181-191. Everest-Dass, A.V., Abrahams, J.L., Kolarich, D., Packer, N.H., and Campbell, M.P. (2013). Structural feature ions for distinguishing N- and O-linked glycan isomers by LC-ESI-IT MS/MS. J Am Soc Mass Spectrom 24, 895-906. Falconer, R.A., Errington, R.J., Shnyder, S.D., Smith, P.J., and Patterson, L.H. (2012). Polysialyltransferase: a new target in metastatic cancer. Curr Cancer Drug Targets 12, 925-939. Finne, J., Krusius, T., and Rauvala, H. (1977). Occurrence of disialosyl groups in glycoproteins. Biochem Biophys Res Commun 74, 405-410. Guile, G.R., Rudd, P.M., Wing, D.R., Prime, S.B., and Dwek, R.A. (1996). A rapid high-resolution high-performance liquid chromatographic method for separating glycan mixtures and analyzing oligosaccharide profiles. Anal Biochem 240, 210-226. Harduin-Lepers, A., Mollicone, R., Delannoy, P., and Oriol, R. (2005). The animal sialyltransferases and sialyltransferase-related genes: a phylogenetic approach. Glycobiology 15, 805-817. Harvey, D.J. (1999). Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates. Mass Spectrom Rev 18, 349-450. Harvey, D.J., Mattu, T.S., Wormald, M.R., Royle, L., Dwek, R.A., and Rudd, P.M. (2002). 'Internal residue loss': rearrangements occurring during the fragmentation of carbohydrates derivatized at the reducing terminus. Anal Chem 74, 734-740. Hayes, C.A., Nemes, S., Issa, S., Jin, C., and Karlsson, N.G. (2012). Glycomic work-flow for analysis of mucin O-linked oligosaccharides. Methods Mol Biol 842, 141-163. Hu, Y., and Mechref, Y. (2012). Comparing MALDI-MS, RP-LC-MALDI-MS and RP-LC-ESI-MS glycomic profiles of permethylated N-glycans derived from model glycoproteins and human blood serum. Electrophoresis 33, 1768-1777. Hu, Y., Zhou, S., Yu, C.Y., Tang, H., and Mechref, Y. (2015). Automated annotation and quantitation of glycans by liquid chromatography/electrospray ionization mass spectrometric analysis using the MultiGlycan-ESI computational tool. Rapid Commun Mass Spectrom 29, 135-142. Jaitly, N., Mayampurath, A., Littlefield, K., Adkins, J.N., Anderson, G.A., and Smith, R.D. (2009). Decon2LS: An open-source software package for automated processing and visualization of high resolution mass spectrometry data. BMC Bioinformatics 10, 87. Julien, S., Bobowski, M., Steenackers, A., Le Bourhis, X., and Delannoy, P. (2013). How Do Gangliosides Regulate RTKs Signaling? Cells 2, 751-767. Karlsson, N.G., Schulz, B.L., and Packer, N.H. (2004). Structural determination of neutral O-linked oligosaccharide alditols by negative ion LC-electrospray-MSn. Journal of the American Society for Mass Spectrometry 15, 659-672. Karlsson, N.G., and Thomsson, K.A. (2009). Salivary MUC7 is a major carrier of blood group I type O-linked oligosaccharides serving as the scaffold for sialyl Lewis x. Glycobiology 19, 288-300. Kawasaki, N., Haishima, Y., Ohta, M., Itoh, S., Hyuga, M., Hyuga, S., and Hayakawa, T. (2001). Structural analysis of sulfated N-linked oligosaccharides in erythropoietin. Glycobiology 11, 1043-1049. Kawasaki, N., Ohta, M., Hyuga, S., Hashimoto, O., and Hayakawa, T. (1999). Analysis of carbohydrate heterogeneity in a glycoprotein using liquid chromatography/mass spectrometry and liquid chromatography with tandem mass spectrometry. Anal Biochem 269, 297-303. Kawashima, H. (2006). Roles of sulfated glycans in lymphocyte homing. Biol Pharm Bull 29, 2343-2349. Khoo, K.H. (2014). From mass spectrometry-based glycosylation analysis to glycomics and glycoproteomics. Adv Neurobiol 9, 129-164. Khoo, K.H., and Yu, S.Y. (2010). Mass spectrometric analysis of sulfated N- and O-glycans. Methods Enzymol 478, 3-26. Kim, Y.J., and Varki, A. (1997). Perspectives on the significance of altered glycosylation of glycoproteins in cancer. Glycoconj J 14, 569-576. Kleene, R., and Schachner, M. (2004). Glycans and neural cell interactions. Nat Rev Neurosci 5, 195-208. Kudelka, M.R., Ju, T., Heimburg-Molinaro, J., and Cummings, R.D. (2015). Simple sugars to complex disease--mucin-type O-glycans in cancer. Adv Cancer Res 126, 53-135. Le Pendu, J., Nystrom, K., and Ruvoen-Clouet, N. (2014). Host-pathogen co-evolution and glycan interactions. Curr Opin Virol 7, 88-94. Lederkremer, G.Z. (2009). Glycoprotein folding, quality control and ER-associated degradation. Curr Opin Struct Biol 19, 515-523. Lemoine, J., Chirat, F., and Domon, B. (1996). Structural analysis of derivatized oligosaccharides using post-source decay matrix-assisted laser desorption/ionization mass spectrometry. J Mass Spectrom 31, 908-912. Lin, C.W., Chen, J.M., Wang, Y.M., Wu, S.W., Tsai, I.H., and Khoo, K.H. (2011). Terminal disialylated multiantennary complex-type N-glycans carried on acutobin define the glycosylation characteristics of the Deinagkistrodon acutus venom. Glycobiology 21, 530-542. Liu, S.W., Chen, C.S., Chang, S.S., Mong, K.K., Lin, C.H., Chang, C.W., Tang, C.Y., and Li, Y.K. (2009a). Identification of essential residues of human alpha-L-fucosidase and tests of its mechanism. Biochemistry 48, 110-120. Liu, T.W., Ho, C.W., Huang, H.H., Chang, S.M., Popat, S.D., Wang, Y.T., Wu, M.S., Chen, Y.J., and Lin, C.H. (2009b). Role for alpha-L-fucosidase in the control of Helicobacter pylori-infected gastric cancer cells. Proc Natl Acad Sci U S A 106, 14581-14586. Magnani, J.L. (2004). The discovery, biology, and drug development of sialyl Lea and sialyl Lex. Arch Biochem Biophys 426, 122-131. Mann, M. (2016). Origins of mass spectrometry-based proteomics. Nat Rev Mol Cell Biol 17, 678-678. Marcos, N.T., Bennett, E.P., Gomes, J., Magalhaes, A., Gomes, C., David, L., Dar, I., Jeanneau, C., DeFrees, S., Krustrup, D., et al. (2011). ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues. Front Biosci (Elite Ed) 3, 1443-1455. Maxwell, E., Tan, Y., Tan, Y., Hu, H., Benson, G., Aizikov, K., Conley, S., Staples, G.O., Slysz, G.W., Smith, R.D., et al. (2012). GlycReSoft: a software package for automated recognition of glycans from LC/MS data. PLoS One 7, e45474. Mechref, Y., Novotny, M.V., and Krishnan, C. (2003). Structural Characterization of Oligosaccharides Using Maldi-TOF/TOF Tandem Mass Spectrometry. Analytical Chemistry 75, 4895-4903. Monteiro, M.A., Appelmelk, B.J., Rasko, D.A., Moran, A.P., Hynes, S.O., MacLean, L.L., Chan, K.H., Michael, F.S., Logan, S.M., O'Rourke, J., et al. (2000). Lipopolysaccharide structures of Helicobacter pylori genomic strains 26695 and J99, mouse model H. pylori Sydney strain, H. pylori P466 carrying sialyl Lewis X, and H. pylori UA915 expressing Lewis B classification of H. pylori lipopolysaccharides into glycotype families. Eur J Biochem 267, 305-320. Monteiro, M.A., Chan, K.H., Rasko, D.A., Taylor, D.E., Zheng, P.Y., Appelmelk, B.J., Wirth, H.P., Yang, M., Blaser, M.J., Hynes, S.O., et al. (1998). Simultaneous expression of type 1 and type 2 Lewis blood group antigens by Helicobacter pylori lipopolysaccharides. Molecular mimicry between h. pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. J Biol Chem 273, 11533-11543. Morelle, W., Faid, V., and Michalski, J.C. (2004). Structural analysis of permethylated oligosaccharides using electrospray ionization quadrupole time-of-flight tandem mass spectrometry and deutero-reduction. Rapid Commun Mass Spectrom 18, 2451-2464. Morgan, R., Gao, G., Pawling, J., Dennis, J.W., Demetriou, M., and Li, B. (2004). N-acetylglucosaminyltransferase V (Mgat5)-mediated N-glycosylation negatively regulates Th1 cytokine production by T cells. J Immunol 173, 7200-7208. Natsuka, S., and Hase, S. (1998). Analysis of N- and O-glycans by pyridylamination. Methods Mol Biol 76, 101-113. Pabst, M., Bondili, J.S., Stadlmann, J., Mach, L., and Altmann, F. (2007). Mass + retention time = structure: a strategy for the analysis of N-glycans by carbon LC-ESI-MS and its application to fibrin N-glycans. Anal Chem 79, 5051-5057. Patel, T., Bruce, J., Merry, A., Bigge, C., Wormald, M., Jaques, A., and Parekh, R. (1993). Use of hydrazine to release in intact and unreduced form both N- and O-linked oligosaccharides from glycoproteins. Biochemistry 32, 679-693. Paulovicova, E., Paulovicova, L., Pilisiova, R., Bystricky, S., Yashunsky, D.V., Karelin, A.A., Tsvetkov, Y.E., and Nifantiev, N.E. (2013). Synthetically prepared glycooligosaccharides mimicking Candida albicans cell wall glycan antigens--novel tools to study host-pathogen interactions. FEMS Yeast Res 13, 659-673. Peltoniemi, H., Natunen, S., Ritamo, I., Valmu, L., and Rabina, J. (2013). Novel data analysis tool for semiquantitative LC-MS-MS2 profiling of N-glycans. Glycoconj J 30, 159-170. Perreault, H., and Costello, C.E. (1999). Stereochemical effects on the mass spectrometric behavior of native and derivatized trisaccharide isomers: comparisons with results from molecular modeling. J Mass Spectrom 34, 184-197. Pilobello, K.T., Krishnamoorthy, L., Slawek, D., and Mahal, L.K. (2005). Development of a lectin microarray for the rapid analysis of protein glycopatterns. Chembiochem 6, 985-989. Pinho, S.S., Figueiredo, J., Cabral, J., Carvalho, S., Dourado, J., Magalhaes, A., Gartner, F., Mendonfa, A.M., Isaji, T., Gu, J., et al. (2013). E-cadherin and adherens-junctions stability in gastric carcinoma: functional implications of glycosyltransferases involving N-glycan branching biosynthesis, N-acetylglucosaminyltransferases III and V. Biochim Biophys Acta 1830, 2690-2700. Pinho, S.S., Reis, C.A., Paredes, J., Magalhaes, A.M., Ferreira, A.C., Figueiredo, J., Xiaogang, W., Carneiro, F., Gartner, F., and Seruca, R. (2009). The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin. Hum Mol Genet 18, 2599-2608. Pinho, S.S., Seruca, R., Gartner, F., Yamaguchi, Y., Gu, J., Taniguchi, N., and Reis, C.A. (2011). Modulation of E-cadherin function and dysfunction by N-glycosylation. Cell Mol Life Sci 68, 1011-1020. Portela, S.V., Martin, C.V., Romay, L.M., Cuevas, E., Martin, E.G., and Briera, A.F. (2011). sLea and sLex expression in colorectal cancer: implications for tumourigenesis and disease prognosis. Histol Histopathol 26, 1305-1316. Ritamo, I., Rabina, J., Natunen, S., and Valmu, L. (2013). Nanoscale reversed-phase liquid chromatography-mass spectrometry of permethylated N-glycans. Anal Bioanal Chem 405, 2469-2480. Robbe-Masselot, C., Herrmann, A., Maes, E., Carlstedt, I., Michalski, J.C., and Capon, C. (2009). Expression of a core 3 disialyl-Le(x) hexasaccharide in human colorectal cancers: a potential marker of malignant transformation in colon. J Proteome Res 8, 702-711. Rudd, P.M., Guile, G.R., Kuster, B., Harvey, D.J., Opdenakker, G., and Dwek, R.A. (1997). Oligosaccharide sequencing technology. Nature 388, 205-207. Satoh, T., Toshimori, T., Yan, G., Yamaguchi, T., and Kato, K. (2016). Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. Scientific Reports 6, 20575. Schnaar, R.L., Gerardy-Schahn, R., and Hildebrandt, H. (2014). Sialic acids in the brain: gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration. Physiol Rev 94, 461-518. Takasaki, S., Mizuochi, T., and Kobata, A. (1982). Hydrazinolysis of asparagine-linked sugar chains to produce free oligosaccharides. Methods Enzymol 83, 263-268. Tateno, H., Ohnishi, K., Yabe, R., Hayatsu, N., Sato, T., Takeya, M., Narimatsu, H., and Hirabayashi, J. (2010). Dual specificity of Langerin to sulfated and mannosylated glycans via a single C-type carbohydrate recognition domain. J Biol Chem 285, 6390-6400. Valladeau, J., Ravel, O., Dezutter-Dambuyant, C., Moore, K., Kleijmeer, M., Liu, Y., Duvert-Frances, V., Vincent, C., Schmitt, D., Davoust, J., et al. (2000). Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12, 71-81. Varki, A., Cummings, R.D., Aebi, M., Packer, N.H., Seeberger, P.H., Esko, J.D., Stanley, P., Hart, G., Darvill, A., Kinoshita, T., et al. (2015). Symbol Nomenclature for Graphical Representations of Glycans. Glycobiology 25, 1323-1324. Varki, A., and Lowe, J.B. (2009). Biological Roles of Glycans. In Essentials of Glycobiology, A. Varki, R.D. Cummings, J.D. Esko, H.H. Freeze, P. Stanley, C.R. Bertozzi, G.W. Hart, and M.E. Etzler, eds. (Cold Spring Harbor (NY)). Viseux, N., de Hoffmann, E., and Domon, B. (1997a). Structural analysis of permethylated oligosaccharides by electrospray tandem mass spectrometry. Anal Chem 69, 3193-3198. Viseux, N., de Hoffmann, E., and Domon, B. (1997b). Structural Analysis of Permethylated Oligosaccharides by Electrospray Tandem Mass Spectrometry. Analytical Chemistry 69, 3193-3198. Viseux, N., de Hoffmann, E., and Domon, B. (1998). Structural Assignment of Permethylated Oligosaccharide Subunits Using Sequential Tandem Mass Spectrometry. Analytical Chemistry 70, 4951-4959. Wang, S.H., Tsai, C.M., Lin, K.I., and Khoo, K.H. (2013). Advanced mass spectrometry and chemical analyses reveal the presence of terminal disialyl motif on mouse B-cell glycoproteins. Glycobiology 23, 677-689. Wang, S.H., Wu, S.W., and Khoo, K.H. (2011). MS-based glycomic strategies for probing the structural details of polylactosaminoglycan chain on N-glycans and glycoproteomic identification of its protein carriers. Proteomics 11, 2812-2829. Wu, S.W., Pu, T.H., Viner, R., and Khoo, K.H. (2014). Novel LC-MS(2) product dependent parallel data acquisition function and data analysis workflow for sequencing and identification of intact glycopeptides. Anal Chem 86, 5478-5486. Wuhrer, M., Deelder, A.M., and Hokke, C.H. (2005). Protein glycosylation analysis by liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 825, 124-133. Wuhrer, M., Koeleman, C.A., and Deelder, A.M. (2009). Two-dimensional HPLC separation with reverse-phase-nano-LC-MS/MS for the characterization of glycan pools after labeling with 2-aminobenzamide. Methods Mol Biol 534, 79-91. Yu, C.Y., Mayampurath, A., Hu, Y., Zhou, S., Mechref, Y., and Tang, H. (2013a). Automated annotation and quantification of glycans using liquid chromatography-mass spectrometry. Bioinformatics 29, 1706-1707. Yu, C.Y., Mayampurath, A., and Tang, H. (2013b). Software tools for glycan profiling. Methods Mol Biol 951, 269-276. Yu, S.Y., Wu, S.W., Hsiao, H.H., and Khoo, K.H. (2009). Enabling techniques and strategic workflow for sulfoglycomics based on mass spectrometry mapping and sequencing of permethylated sulfated glycans. Glycobiology 19, 1136-1149. Yu, S.Y., Wu, S.W., and Khoo, K.H. (2006). Distinctive characteristics of MALDI-Q/TOF and TOF/TOF tandem mass spectrometry for sequencing of permethylated complex type N-glycans. Glycoconj J 23, 355-369. Zaia, J. (2004). Mass spectrometry of oligosaccharides. Mass Spectrom Rev 23, 161-227. Zhao, Y., Sato, Y., Isaji, T., Fukuda, T., Matsumoto, A., Miyoshi, E., Gu, J., and Taniguchi, N. (2008). Branched N-glycans regulate the biological functions of integrins and cadherins. FEBS J 275, 1939-1948. Zhou, S., Hu, Y., and Mechref, Y. (2016). High-temperature LC-MS/MS of permethylated glycans derived from glycoproteins. Electrophoresis 37, 1506-1513. Zielinska, D.F., Gnad, F., Wisniewski, J.R., and Mann, M. (2010). Precision mapping of an in vivo N-glycoproteome reveals rigid topological and sequence constraints. Cell 141, 897-907. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76613 | - |
| dc.description.abstract | 細胞表面的醣基化修飾存在於不同的醣蛋白及醣脂質上，其多樣性的醣結構組合而成的醣質體已知在生物體中扮演極為重要的功能與角色。例如，醣質體的末端表位參與細胞間的相互辨識，或是生物分子間藉由醣質體與凝集素而連結，以及疾病相關的病原體藉由細胞表面的醣質體所造成感染，除此之外，癌症的發生往往也伴隨著不正常的醣化表現。醣類的結構組成，主要是由固定的核心次單元進行延伸，藉由不同醣鏈骨架的延長、分支，以及末端醣的修飾所組成，其結構的最末端稱之為醣質體末端表位，這也是生物系統中辨識醣質體最重要的決定位置。因此，建立高效率的醣質體分析平台，使之精準地分析其末端表位的結構是極其重要的。隨著儀器的日新月異，新世代的質譜儀可集合不同感測器及碰撞室功能於單一儀器，可在不同的分析組合下提高檢測速度，並提供不同斷片模式於多次質譜分析，進而提高了獲得有用醣斷片資訊的可能性。由於醣質體及其個別結構無模板可供預測，不像蛋白質體的質譜分析，可以利用水解後的胜肽進行質譜斷裂，再以軟體快速比對序列資料，因此醣質體質的質譜分析缺少相對應的軟體及資料庫也將是分析上的另一個挑戰。
本論文的研究工作主旨即在於(一)利用新世代高解析液相層析串聯質譜儀結合蛋白質體研究的層析方法，在不更換溶液及管柱前提下，完成利用不同電性切換，探討不同樣品間的醣質體及其特定(硫酸化)醣末端表位分析。(二)配合質譜儀及方法的演進，同時進行軟體開發，用以處理大量的質譜數據並分析出有用的醣質體資訊；並配合不同質譜檢測及不同儀器參數或不同的醣類樣品，開發其對應的功能及參數，及找出定性及相對定量方法。(三)利用此平台分析不同生物樣品的醣質體變化及發現相對少量的末端表位，在利用胃癌細胞醣質體為受質的研究中，成功發現不同岩藻糖苷酵素對特定端岩藻糖末端表位具有不同專一性，以及分析老鼠紋狀體組織醣質體發現含少見的雙唾液酸末端表位。 本論文已完成醣質體末端表位鑑定平台開發，包含整合高解析醣質體的質譜技術及高通量的數據分析。故此平台將可應用於不同生物樣品的體醣質分析，及利用實驗設計用以分析在不同生理條件、不同基因表現和不同化學作用下的醣質體變化。隨著新世代高解析質譜儀和醣質體生物資訊的快速發展，結合次世代基因定序科技及其他科學研究，可讓疾病的預防與診療能夠更為精準，以期達到精準醫療的最終目標。 | zh_TW |
| dc.description.abstract | Glycans attached on lipid and proteins mediate a variety of structural and functional roles in cell–cell recognition, cell-matrix adhesion and host-pathogen interactions. Aberrant glycosylation has been implicated in the development of diseases such as cancer. N- or O-glycans have common core structures which can be extended either in linear or branched form, and are then modified or terminally capped by sialic acid, fucose, and sulfate at different positions to generate the critical terminal glyco-epitopes, or glycotopes. To better address their biological functions, it is essential to develop a precise glycomic analytical platform that will globally survey the tremendously heterogeneous glycan structures expressed by a cell to seek out, identify and quantify the all-important glycotopes. This is made possible by the advent of Orbitrap Fusion Tribrid mass spectrometer system, which combines quadrupole, Orbitrap, and ion trap mass analyzers, with increasing speed of HCD and CID fragmentation that can be performed in parallel or in successive stages for maximum experimental flexibility. Taking advantages of these latest advances in mass spectrometry (MS), the primary goal of this thesis work is to establish a high throughput glycotope-centric glycomics workflow based on nanoLC-MS2-product dependent-MS3 analysis of permethylated glycans. Such nanoLC-MS2/MS3 data acquisition mode was previously shown to be effective for mapping the sulfated glycotopes in negative ion mode, and now extended in this work to distinguish closely related isomeric fucosylated glycotopes carried on non-sulfated glycans in positive ion mode. The diagnostic MS3 ions were validated via analysis of glycan standards while the reverse phase C18 nanoLC conditions were optimized by running against complex glycomic samples derived from gastric and colon cancer cell lines. With elevated temperature, isomeric constituents of smaller O-glycans were shown to be well resolved but not those of larger size carrying increasing numbers of fucose, sialic acids and sulfates. To facilitate data analysis, a data mining computational tool, GlyPick, was developed and implemented at various levels to filter out true glycan MS2 spectra and associated MS3 triggered on target glycotopes; to search for, identify and quantify their relative amount based on the summed intensity of the diagnostic MS2/MS3 ions to allow comparison across different samples; as well as to assign glycosyl compositions to inferred monoisotopic precursors and to quantify their relative abundance, in a fully automated fashion. Finally, the established glycotope-centric glycomics workflow was applied to 1) map the glycomic changes in gastric fucosylated glycotopes in response to treatments by fucosidases of distinct specificities; 2) search for and identify with confident rare disialylated glycotopes on the N-glycans from mouse brain striatum. The demonstrated practical utilities of this novel analytical platform will allow high sensitivity in depth glycomic mapping that can parallel the progress in applying next-generation sequencing (NGS) and proteomics to precision medicine for disease treatment and prevention that takes into account individual variability. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:33:53Z (GMT). No. of bitstreams: 1 ntu-106-D00b46006-1.pdf: 23446785 bytes, checksum: 563eb75370a81a5b5602d0f3650481e7 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | Chapter 1. Introduction
1.1 Glycosylation…………………..………………………………………………………………………………….….1 1.2 Structural diversity in N- and O-glycans……………………………………………………….….…..…2 1.2.1 Terminal ABO structures and Lewis glycotopes…………………………………………………3 1.2.2 Disialic acid (DiSia) and polysialic acid (PSA) epitopes……………………………..…..…..4 1.2.3 Sulfated glycotopes……………………………………………………………………….……….………..5 1.3 Biological roles of glycans……………………………………………………………………..…….…………6 1.4 Precision glycomics…………………………………………………………………………….……….…………8 1.5 Mass Spectrometry (MS)-based Glycomics………………………………………………….……….10 1.6 LC-MS approaches for glycan analysis……………………………………………….………….……...11 1.6.1 Fluorescent tagged glycans followed by HPLC with or without MS analysis….…12 1.6.2 Native glycans separated by porous graphitized carbon (PGC) column and analyzed by ESI-MS/MS……………………………………………………………………..….……….13 1.6.3 Permethylated glycans separated by reversed-phase column and analyzed by ESI-MS/MS (presented in this thesis) ………………………………………………….….………14 1.7 MS/MS sequencing of permethylated glycans………………………………………….…………..15 1.8 New-generation mass spectrometer……………………………………………………….………......19 1.9 Glycoinformatics tools for LC-MS/MS data mining………………………………..……………..21 1.10 Specific aims………………………………………………………………………………………………………26 Chapter 2. Materials and Methods 2.1 Cells, enzymes and reagents……………………………………………………..……………….…………29 2.2 Mouse striatum tissues…………………………………………………………….………………….………31 2.3 Glycan release and permethylation…………………………………………………..………….………31 2.4 NanoLC-MS/MS systems…………………………………………………………………….………….…….32 2.5 GlyPick software development………………………….…………………………………………….……34 Chapter 3. Results 3.1 Characteristic features of RP nanoLC-MS/MS of permethylated glycans………...……36 3.2 The development of data mining tool “GlyPick” for LC-MS/MS workflow………....…48 3.3 Identification and relative quantification of target glycotopes facilitated by GlyPick…………………………………………………………………………………………………………..……..……57 3.4 Mining of sulfated glycotopes by GlyPick………………………………………………..…….….….70 3.5 Fitting glycosyl composition by GlyPick to facilitate glycan structure assignment…73 3.6 Identifying rare disialylated glycotopes facilitated by GlyPick……………………….………78 Chapter 4. Conclusion and Future Perspective……………….………………………………….………88 References……………………………………………………………………………………………………….…..……90 Abbreviations…………………………………………………………………………………………………………….99 List Figures Figure 1.1 Common classes of glycoconjugates in mammalian cells…………………………..…2 Figure 1.2 Structural features of N- and O-linked Glycans…………………………………………....3 Figure 1.3 Schematic representation of the terminal ABH structures and Lewis epitopes…………………………………………………………….…………………………………………………………4 Figure 1.4 Various commonly occurring sulfated glycotopes………………………………..………5 Figure 1.5 General Roles of Glycans in Glycoprotein…………………………….………………………6 Figure 1.6 Glycotope-Centric Glycomics……………………………………………………………………….9 Figure 1.7 LC-MS2-pd-MS3 analysis of sodiated permethylated Lewis/H glycotopes in LTQ-Orbitrap Elite……………………………………………………………….………………………………..……15 Figure 1.8 CID MS/MS fragmentation pathways for permethylated glycans…………...…16 Figure 1.9 Characteristic low mass HCD fragment ions for determination of the location of sulfate on terminal glycotopes………………………………………….………………………….……..…17 Figure 1.10 Product-dependent (Pd) MS3 to distinguish with type 1 and type 2 glycotopes……………………………………………………………………………………………………………….…18 Figure 1.11 LC-MS2-pd-MS3 analysis of protonated permethylated Lewis B/Y glycotopes in different generations of the Orbitrap series mass spectrometers…………….…….…..…19 Figure 1.12 Schematic of the LTQ-Orbitrap Elite Hybrid MS………………………………..…..…20 Figure 1.13 Schematic of the Orbitrap Fusion Tribrid MS………………………………….…..……21 Figure 1.14 GlyPick-A glycoinformatics tool to facilitate mining of LC‐MS2-pd-MS3 dataset………………………………………………………………………………………………………….….…….…25 Figure 1.15 Overview of LC-MS analysis and GlyPick Data Mining workflow……….……..26 Figure 3.1 Characteristic MS2/MS3 spectra and ions generated from permethylated glycan standards carrying the target glycotopes………………………………..…………….………..39 Figure 3.2 Overview of a Glycotope centric LC-MS/MS-based glycomic workflow using the Orbitrap Fusion™ Tribrid™ system…………………………………..…………….…………………...40 Figure 3.3 Exemplary HCD-MS2 of permethylated, neutral O-glycans and pd-CID-MS3 of fucosylated terminal glycotopes…………………………………………………………….………………….41 Figure 3.4 Exemplary CID-MS2 of permethylated, monosulfated O-glycans and pd-HCD-MS3 of monosulfated terminal glycotopes……………………………………….………..……….…..…42 Figure 3.5 RP C18 nanoLC separation and MS2/MS3 identification of permethylated, non-fucosylated and mono-fucosylated, single LacNAc-extended Core 1 and Core 2 O-glycan structures………………………………………………………………………………………………..………43 Figure 3.6 RP C18 nanoLC separation of permethylated T, ST, Tn, and STn antigens derived from AGC cells………………………………………………………………….……………….………….44 Figure 3.7 Limitation of chromatographic resolution for large permethylated O-glycans using C18 reversed-phase chromatography…………………………………………………..…..………45 Figure 3.8 RP C18 nanoLC separation of permethylated LacNAc1-2-extended cores 1 and 2 O-glycans with 0-2 Fuc……………………………………………………….……………………..……..46 Figure 3.9 RP C18 nanoLC separation of permethylated high mannose type and bi-antennary complex type N-glycans……………………………………………………..……………..………47 Figure 3.10 High-resolution accurate mass (HR/AM) spectra facilitates GlyPick data mining………………………………………………………………………………………………..……..………………49 Figure 3.11 Graphical User Interface (GUI) for GlyPick………………………..…………..…………50 Figure 3.12 GlyPick Parameter Settings for MS2………………………………………….……………..50 Figure 3.13 GlyPick Parameter Settings for MS1…………………………………………..…………….51 Figure 3.14 GlyPick Parameter Settings for MS3…………………………………………….…………..52 Figure 3.15 Identification of terminal glycotopes and their relative quantification based on diagnostic MS2/MS3 ions………………………………..……………………………………………....…….60 Figure 3.16 Summed ion intensities for individual MS2 diagnostic ions across 10 fold differences in applied sample amount of permethylayted AGS O-glycans…………...…….62 Figure 3.17 Accessing the glycomic impact of human fucosidase FUCA1 and FUCA2 digestions on the constituent fucosylated glycotopes of AGS O-glycans……………..…..…69 Figure 3.18 Trap CID-MS2 and HCD-MS3 spectra of select permethylated, sulfated O-glycans to demonstrate how individual sulfated O-glycans can be identified…………....71 Figure 3.19 LC-MS2-pd-MS3 analysis of permethylated sulfated AGS O-glycans…………72 Figure 3.20 Glycotope-centric glycomic analysis of N-glycans from mouse brain striatum………………………………………………………………………………………………………………..……82 Figure 3.21 LC-MS2-PD-MS3 analysis of Disialyl acid LacNAc glycotopes from N-Glycan derived from mouse brain tissues………………………………………………………………….……..……83 Figure 3.22 An overlapping isotopic cluster for co-eluting N-glycans………………….………84 List of Tables Table 3.1 MS2 fragment ions of non-sulfated protonated glycan by CID/HCD MS2 in positive ion mode………………………………………………………………………………………………………53 Table 3.2 MS2 fragment ions of non-sulfated sodiated glycan by CID MS2 in positive ion mode……………………………………………………………………………………………………………….……..…54 Table 3.3 MS2 fragment ions of sulfated glycan by CID/HCD MS2 in negative ion mode…………………………………………………………………………………………………………………….…..55 Table 3.4 Characteristic ions for glycotopes deduced by HCD-MS2 and pd-CID-MS3.….56 Table 3.5 Data and Statistics for Glycotope Identification and Relative Quantification by MS2/MS3 ion intensities………………………………………………………………………………….…….……64 Table 3.6 Triplicate Reproducibility of Glycotope Identification and Relative Quantification by MS2/MS3 ion intensities…………………………………………………………….……67 Table 3.7 LC-MS2/MS3 Dataset on permethylated sulfated AGS O-Glycans…………….….75 Table 3.8 LC-MS2-pd-MS3 data for the permethylated N-glycans of mouse brain striatum…………………………………………………………………………………………………………….……….85 | |
| dc.language.iso | en | |
| dc.subject | 醣質生物資訊 | zh_TW |
| dc.subject | 醣質體 | zh_TW |
| dc.subject | 醣質體末端表位 | zh_TW |
| dc.subject | 高解析液相層析串聯質譜儀 | zh_TW |
| dc.subject | 精準醫療 | zh_TW |
| dc.subject | Glycoinformatics | en |
| dc.subject | LC?MS | en |
| dc.subject | Orbitrap Fusion | en |
| dc.subject | Glycomics | en |
| dc.subject | Glycotopes | en |
| dc.subject | Precison medicine | en |
| dc.title | 以高階液相層析串聯質譜分析技術研發高通量醣質體末端表位鑑定平台 | zh_TW |
| dc.title | Advancing a High Throughput Glycotope-Centric Glycomics Workflow Based on NanoLC-MS2-Product Dependent-MS3 Analysis of Permethylated Glycans | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 陳頌方,張權發,陳逸然,蕭鶴軒 | |
| dc.subject.keyword | 醣質體,醣質體末端表位,高解析液相層析串聯質譜儀,醣質生物資訊,精準醫療, | zh_TW |
| dc.subject.keyword | Glycomics,Glycotopes,LC?MS,Orbitrap Fusion,Glycoinformatics,Precison medicine, | en |
| dc.relation.page | 99 | |
| dc.identifier.doi | 10.6342/NTU201700295 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2017-02-05 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-D00b46006-1.pdf 未授權公開取用 | 22.9 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。