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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 邱繼輝(Kay-Hooi Khoo) | |
| dc.contributor.author | Huan-Chuan Tseng | en |
| dc.contributor.author | 曾煥權 | zh_TW |
| dc.date.accessioned | 2021-06-16T04:06:57Z | - |
| dc.date.available | 2021-12-31 | |
| dc.date.copyright | 2020-08-14 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-07-29 | |
| dc.identifier.citation | Angata, T., Nakata, D., Matsuda, T., Kitajima, K., Troy, F. A., 2nd. (1999). Biosynthesis of KDN (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid). Identification and characterization of a KDN-9-phosphate synthetase activity from trout testis. J Biol Chem, 274(33), 22949-22956. doi:10.1074/jbc.274.33.22949 Anumula, K. R., Taylor, P. B. (1992). A comprehensive procedure for preparation of partially methylated alditol acetates from glycoprotein carbohydrates. Analytical Biochemistry, 203(1), 101-108. doi:https://doi.org/10.1016/0003-2697(92)90048-C Avsar-Ban, E., Ishikawa, H., Manya, H., Watanabe, M., Akiyama, S., Miyake, H., . . . Tamaru, Y. (2010). Protein O-mannosylation is necessary for normal embryonic development in zebrafish. Glycobiology, 20(9), 1089-1102. doi:10.1093/glycob/cwq069 Baskin, J. M., Dehnert, K. W., Laughlin, S. T., Amacher, S. L., Bertozzi, C. R. (2010). Visualizing enveloping layer glycans during zebrafish early embryogenesis. Proc Natl Acad Sci U S A, 107(23), 10360-10365. doi:10.1073/pnas.0912081107 Bause, E., Legler, G. (1981). The role of the hydroxy amino acid in the triplet sequence Asn-Xaa-Thr(Ser) for the N-glycosylation step during glycoprotein biosynthesis. Biochemical Journal, 195(3), 639-644. doi:10.1042/bj1950639 Bowman, K. G., Bertozzi, C. R. (1999). Carbohydrate sulfotransferases: mediators of extracellular communication. Chemistry Biology, 6(1), R9-R22. doi:https://doi.org/10.1016/S1074-5521(99)80014-3 Cabezas-Cruz, A., Espinosa, P. J., Alberdi, P., Simo, L., Valdes, J. J., Mateos-Hernandez, L., . . . de la Fuente, J. (2018). Tick galactosyltransferases are involved in alpha-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development. Sci Rep, 8(1), 14224. doi:10.1038/s41598-018-32664-z Chang, L. Y., Harduin-Lepers, A., Kitajima, K., Sato, C., Huang, C. J., Khoo, K. H., Guerardel, Y. (2009). Developmental regulation of oligosialylation in zebrafish. Glycoconj J, 26(3), 247-261. doi:10.1007/s10719-008-9161-5 Cheng, C. W., Chou, C. C., Hsieh, H. W., Tu, Z., Lin, C. H., Nycholat, C., . . . Khoo, K. H. (2015). Efficient Mapping of Sulfated Glycotopes by Negative Ion Mode nanoLC-MS/MS-Based Sulfoglycomic Analysis of Permethylated Glycans. Anal Chem, 87(12), 6380-6388. doi:10.1021/acs.analchem.5b01409 Ciucanu, I., Kerek, F. (1984). A simple and rapid method for the permethylation of carbohydrates. Carbohydrate Research, 131(2), 209-217. doi:https://doi.org/10.1016/0008-6215(84)85242-8 Dell, A., Thomas-Oates, J. E., Rogers, M. E., Tiller, P. R. (1988). Novel fast atom bombardment mass spectrometric procedures for glycoprotein analysis. Biochimie, 70(11), 1435-1444. doi:https://doi.org/10.1016/0300-9084(88)90280-5 Dwyer, C. A., Katoh, T., Tiemeyer, M., Matthews, R. T. (2015). Neurons and glia modify receptor protein-tyrosine phosphatase zeta (RPTPzeta)/phosphacan with cell-specific O-mannosyl glycans in the developing brain. J Biol Chem, 290(16), 10256-10273. doi:10.1074/jbc.M114.614099 Flanagan-Steet, H. R., Steet, R. (2013). 'Casting' light on the role of glycosylation during embryonic development: insights from zebrafish. Glycoconj J, 30(1), 33-40. doi:10.1007/s10719-012-9390-5 Fukuda, M., Hiraoka, N., Akama, T. O., Fukuda, M. N. (2001). Carbohydrate-modifying sulfotransferases: structure, function, and pathophysiology. J Biol Chem, 276(51), 47747-47750. doi:10.1074/jbc.R100049200 Guérardel, Y., Chang, L.-Y., Maes, E., Huang, C.-J., Khoo, K.-H. (2005). Glycomic survey mapping of zebrafish identifies unique sialylation pattern. Glycobiology, 16(3), 244-257. doi:10.1093/glycob/cwj062 Guerardel, Y., Chang, L. Y., Maes, E., Huang, C. J., Khoo, K. H. (2006). Glycomic survey mapping of zebrafish identifies unique sialylation pattern. Glycobiology, 16(3), 244-257. doi:10.1093/glycob/cwj062 Hanzawa, K., Suzuki, N., Natsuka, S. (2017). Structures and developmental alterations of N-glycans of zebrafish embryos. Glycobiology, 27(3), 228-245. doi:10.1093/glycob/cww124 Hemmerich, S. (2001). Carbohydrate sulfotransferases: novel therapeutic targets for inflammation, viral infection and cancer. Drug Discovery Today, 6(1), 27-35. doi:https://doi.org/10.1016/S1359-6446(00)01581-6 Hsiao, C. T., Wang, P. W., Chang, H. C., Chen, Y. Y., Wang, S. H., Chern, Y., Khoo, K. H. (2017). Advancing a High Throughput Glycotope-centric Glycomics Workflow Based on nanoLC-MS(2)-product Dependent-MS(3) Analysis of Permethylated Glycans. Mol Cell Proteomics, 16(12), 2268-2280. doi:10.1074/mcp.TIR117.000156 Jiang, K., Zhu, H., Li, L., Guo, Y., Gashash, E., Ma, C., . . . Wang, P. G. (2017). Sialic acid linkage-specific permethylation for improved profiling of protein glycosylation by MALDI-TOF MS. Anal Chim Acta, 981, 53-61. doi:10.1016/j.aca.2017.05.029 Kang, P., Mechref, Y., Klouckova, I., Novotny, M. V. (2005). Solid-phase permethylation of glycans for mass spectrometric analysis. Rapid Commun Mass Spectrom, 19(23), 3421-3428. doi:10.1002/rcm.2210 Karlsson, N. G., Wilson, N. L., Wirth, H. J., Dawes, P., Joshi, H., Packer, N. H. (2004). Negative ion graphitised carbon nano-liquid chromatography/mass spectrometry increases sensitivity for glycoprotein oligosaccharide analysis. Rapid Commun Mass Spectrom, 18(19), 2282-2292. doi:10.1002/rcm.1626 Khoo, K.-H., Yu, S.-Y. (2010). Chapter One - Mass Spectrometric Analysis of Sulfated N- and O-Glycans. In M. Fukuda (Ed.), Methods in Enzymology (Vol. 478, pp. 3-26): Academic Press. Laughlin, S. T., Baskin, J. M., Amacher, S. L., Bertozzi, C. R. (2008). In Vivo Imaging of Membrane-Associated Glycans in Developing Zebrafish. Science, 320(5876), 664-667. doi:10.1126/science.1155106 Maeda, Y., Kinoshita, T. (2008). Dolichol-phosphate mannose synthase: structure, function and regulation. Biochim Biophys Acta, 1780(6), 861-868. doi:10.1016/j.bbagen.2008.03.005 Pabst, M., Altmann, F. (2011). Glycan analysis by modern instrumental methods. Proteomics, 11(4), 631-643. doi:10.1002/pmic.201000517 Souza, A. R., Kozlowski, E. O., Cerqueira, V. R., Castelo-Branco, M. T., Costa, M. L., Pavao, M. S. (2007). Chondroitin sulfate and keratan sulfate are the major glycosaminoglycans present in the adult zebrafish Danio rerio (Chordata-Cyprinidae). Glycoconj J, 24(9), 521-530. doi:10.1007/s10719-007-9046-z Takemoto, T., Natsuka, S., Nakakita, S.-i., Hase, S. (2005). Expression of complex-type N-glycans in developmental periods of zebrafish embryo. Glycoconjugate Journal, 22(1), 21-26. doi:10.1007/s10719-005-0189-5 Vanbeselaere, J., Chang, L. Y., Harduin-Lepers, A., Fabre, E., Yamakawa, N., Slomianny, C., . . . Guerardel, Y. (2012). Mapping the expressed glycome and glycosyltransferases of zebrafish liver cells as a relevant model system for glycosylation studies. J Proteome Res, 11(4), 2164-2177. doi:10.1021/pr200948j Varki., A., Cummings., R. D., Esko., J. D., Stanley., P., Hart., G. W., Aebi., M., . . . Seeberger, P. H. (2017). Essentials of Glycobiology(3rd ed.). Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK310274/ Yamakawa, N., Vanbeselaere, J., Chang, L. Y., Yu, S. Y., Ducrocq, L., Harduin-Lepers, A., . . . Guerardel, Y. (2018). Systems glycomics of adult zebrafish identifies organ-specific sialylation and glycosylation patterns. Nat Commun, 9(1), 4647. doi:10.1038/s41467-018-06950-3 Yu, S.-Y., Wu, S.-W., Hsiao, H.-H., Khoo, K.-H. (2009). Enabling techniques and strategic workflow for sulfoglycomics based on mass spectrometry mapping and sequencing of permethylated sulfated glycans. Glycobiology, 19(10), 1136-1149. doi:10.1093/glycob/cwp113 Yu, S. Y., Chang, L. Y., Cheng, C. W., Chou, C. C., Fukuda, M. N., Khoo, K. H. (2013). Priming mass spectrometry-based sulfoglycomic mapping for identification of terminal sulfated lacdiNAc glycotope. Glycoconj J, 30(2), 183-194. doi:10.1007/s10719-012-9396-z | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55517 | - |
| dc.description.abstract | 隨著質譜儀器與電腦運算技術的進步，對於不同物種、器官、細胞或疾病進行醣質體學與醣蛋白體學分析，進而嘗試闡述其生物功能意義的研究方式，是近年生命科學愈受重視的一新興領域。除了以人類為主的醣質體學研究以外，科學家們也研究其他物種所表現的醣質，試圖建立各種模型來探討並解決人體中與醣相關的疾病、生物途徑與機制，藉此提升人類的醫學知識，增進社會福祉。本碩士論文的研究工作，意旨針對斑馬魚的腦、腸與卵巢，以更高精確度與高感度的液相層析串聯式質譜儀分析法，進一步解析鑑定其蛋白醣質體的特色，建構深度的醣末端分子表位於各組織器官的表現分佈圖譜。其中一重點在於首度探討斑馬魚的硫酸化醣質，利用了固相萃取法，將甲基化衍生後帶負電的硫酸化醣質分離出來，再透過自動化質譜圖數據擷取與後續多面向篩選統整分析，鑑定其主要結構、硫酸化位點與相對表現量。主要具體研究成果除發現並解構了斑馬魚腦部與腸特有的唾液酸及硫酸化醣質體表位，首次在腦中找到O-醣基化的甘露醣鏈，印證了斑馬魚體內具有製造O-醣基化甘露醣鏈的相關酵素表現的文獻報導；並在N-醣基化醣鏈上以質譜的方式證實帶有硫酸化修飾的人類自然殺手-1(HNK-1)末端表位結構，交互驗證了先前其他研究團隊透過抗體染色推論斑馬魚腦內的人類自然殺手-1抗原的表現。由於小鼠與人類的腦中皆有類似的末端表位以及O、N-醣基化的多醣鏈表現，透過全面性地研究斑馬魚的醣質體，以期能幫助學界在未來研究醣生物學相關的生理功能與疾病時，建立一個相對於小鼠或人類而言便利、成本低廉、更符合需求的斑馬魚替代模型。 | zh_TW |
| dc.description.abstract | Driven largely by recent technical advances in mass spectrometry, glycomics is increasingly being pursued. It raises our knowledge and provides evidence for one of the most fascinating post-translational modifications, which adds glycans onto proteins and alters their functions. Danio rerio (zebrafish) is one of model organisms that is well-suited for genetic and developmental studies, serving in many instances as relevant disease models that offer many advantages besides mouse model. Current understanding of the embryos and adult zebrafish glycomes indicates high similarity with, as well as distinctive differences from that of human and mice. Similarities on gene level as paralogous genes are also high, which may be exploited as keys to uncover glycosylation-associated pathologies in human. Previous structural studies on the zebrafish glycome, by ways of MALDI MS and MS/MS and other techniques in organ-specific manner has provided a broad distribution map of a diverse range of N-, O-GalNAc and lipid-linked glycans but many details are still missing. In my thesis work, the settings and applicability of a higher sensitivity and precision nanoLC-MS2/MS3 platform to non-mammals e.g. zebrafish were first investigated and then fine-tuned to home in on delineating the various unique fucosylated, sialylated, and/or sulfated terminal glycotopes, particularly those expressed in adult brain, in comparison with ongoing comprehensive murine brain glycomics currently undertaken in the laboratory by others. Notably, the presence of sulfated HNK-1 glycotope as carried on sialylated N-glycans in brain was unambiguously identified by the first ever sulfoglycomics performed on zebrafish. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T04:06:57Z (GMT). No. of bitstreams: 1 U0001-2907202021163800.pdf: 16765507 bytes, checksum: 31fa9a92c507879c271883474aa1fd5b (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 序言 ......................................................................i 中文摘要 ..................................................................ii English abstract ..........................................................................iii Chapter 1 Introduction 1.1 Glycosylation as one of PTM in livings ................................1 1.2 Type of glycans in vertebrates ........................................2 1.3 Terminal glycotopes ...................................................5 1.4 Glycome analysis ......................................................8 1.4.1 From glycans to glycome .............................................8 1.4.2 Mass spectrometry-based glycomics ...................................9 1.5 Zebrafish glycome: A model organism for glycomic research .............11 1.5.1 Genomic and research backgrounds of zebrafish N- and O-glycome.......11 1.5.2 Overview of the glycomic profiles of zebrafish ......................12 1.6 Issues unsolved in zebrafish glycomics ................................14 1.7 Specific aims .........................................................16 Chapter 2 Materials and methods 2.1 Materials ...........................................................................17 2.1.1 Zebrafish ...........................................................17 2.1.2 Reagents ...........................................................................17 2.2 Methods ...........................................................................18 2.2.1 Preparing N- and O-glycans for MS analyses ..........................18 2.2.1.1 Extracting glycoproteins and release of N-glycans .................18 2.2.1.2 Separating N-glycans from peptide mixture .........................19 2.2.1.3 Release of O-glycans by β-elimination .............................19 2.2.1.4 Reduce the N-glycans ..............................................20 2.2.2 Site-specific sialic acid permethylation (SSAP) of glycans ..........20 2.2.3 Permethylation of glycans and enrichment of sulfated glycans ........22 2.2.4 Clean-up of glycans prior to MS analysis ............................23 2.2.5 MALDI-TOF/TOF MS and MS/MS analysis .................................23 2.2.6 nanoLC-nanoESI-MS/MS analysis .......................................24 2.2.7 Data mining with Glypick software ...................................27 Chapter 3. Results 3.1 Validate sample consistency through MALDI-TOF-MS ......................29 3.2 Glycomic analysis of permethylated non-sulfated glycans on nanoLC-ESI-MS platform ....................................................31 3.2.1 Permethylated non-sulfated NG .......................................31 3.2.2 Permethylated non-sulfated OG .......................................35 3.3 Glycomic analysis of negatively charged glycans via MALDI-MS ..........40 3.3.1 Brain Intestine E1 and E2 NG by MALDI-MS analysis .................40 3.3.2 Brain Intestine E1 OG by MALDI-MS analysis ........................42 3.4 Glycomic analysis of negatively charged glycans by LC-ESI-MS/MS .......45 3.4.1 Brain Intestine E2 NGs by LC-ESI-MS/MS analysis ...................46 3.4.2 Brain Intestine E1 OG by LC-ESI-MS/MS analysis ....................47 3.4.3 Relative quantitation of sulfated glycotopes ........................48 3.5 HNK-1 epitope in brain NG .............................................54 3.6 Sialic acid linkage in brain NG and OG ................................56 3.7 Brain O-Mannose ...........................................................................58 Chapter 4. Summary and Discussion 4.1 Summary ...............................................................60 4.2 Future Development ....................................................62 References.................................................................66 Abbreviation table ........................................................69 Glycan symbols shown in this thesis .......................................70 List of Figures Fig 1.1 Types of N-glycans .................................................3 Fig 1.2 Typical complex type structures of N-glycans .......................3 Fig 1.3 Types of extended O-GalNAc glycan ..................................4 Fig 1.4 Type-1, -2, and -3 H, A, and B antigens that form the O (H), A, and B blood group determinants on N- and O-glycans .........................7 Fig 1.5 Type-1 and -2 Lewis determinants. ..................................8 Fig 1.6 Structures of three different kinds of sialic acids ................8 Fig 1.7 Structural information of general sialylated terminal glycotopes and zebrafish-specific glycotopes..............................................14 Fig 2.1 Schematic view of sialic linkage specific derivatization ..........21 Fig 3.1 MALDI spectra of zebrafish non-sulfated NGs and OGs ...............30 Fig 3.2 XICs of non-sulfated NGs in three of zebrafish tissues ............33 Fig 3.3 MS2/MS3 spectra of representative NGs and relative quantitation of terminal glycotopes ................................................................34 Fig 3.4 XICs of non-sulfated OGs in three of zebrafish tissues ............38 Fig 3.5 MS2/MS3 spectra of representative OGs and relative quantitation of terminal glycotopes ................................................................39 Fig 3.6 MALDI spectra of zebrafish sulfated NGs and OGs ...................44 Fig 3.7 XICs of di-suflated NGs and sulfated OGs in zebrafish .............49 Fig 3.8 MS2/MS3 spectra of representative sulfated NGs and OGs ............50 Fig 3.9 Relative quantitation of the sulfated glycotopes ..................53 Fig 3.10 MALDI MS/MS and LC-ESI-MS/MS of HNK-1 epitope in zebrafish .......55 Fig 3.11 MALDI spectra of SSAP derivatized zebrafish non-sulfated and sulfated brain NGs and OGs ................................................57 Fig 3.12 XICs and MS2/MS3 spectra of O-mannose glycans in zebrafish brain .59 List of Tables Table 2.1 Experiment samples used in this article. ........................17 Table 2.2 Ion list for non-sulfated NGs and OGs triggering pdMS3 ..........27 | |
| dc.language.iso | en | |
| dc.subject | 液相層析串聯式質譜儀 | zh_TW |
| dc.subject | 斑馬魚（硫酸化）醣質體學 | zh_TW |
| dc.subject | 末端醣表位 | zh_TW |
| dc.subject | 人類自然殺手-1 | zh_TW |
| dc.subject | zebrsfish (sulfo-) glycomics | en |
| dc.subject | nanoLC-MS/MS | en |
| dc.subject | terminal glycotope | en |
| dc.subject | HNK-1 epitope | en |
| dc.title | 基於液相層析質譜平台的醣質體分析方法對成年斑馬魚的器官特異之末端醣表位的深入詮釋 | zh_TW |
| dc.title | Further delineation of organ-specific terminal glycotopes of adult zebrafish by LC-MS/MS-based glycomics | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 洪上程(Shang-Cheng Hung),徐翠玲(Tsui-Ling Hsu) | |
| dc.subject.keyword | 斑馬魚（硫酸化）醣質體學,液相層析串聯式質譜儀,末端醣表位,人類自然殺手-1, | zh_TW |
| dc.subject.keyword | zebrsfish (sulfo-) glycomics,nanoLC-MS/MS,terminal glycotope,HNK-1 epitope, | en |
| dc.relation.page | 70 | |
| dc.identifier.doi | 10.6342/NTU202002060 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-07-30 | |
| 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 | |
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