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研究生: 郭力禎
Guo, Li-Jhen
論文名稱: 酵素唾液酸化 Globo-系列醣體
Enzymatic Sialylation of Globo-Series Glycans
指導教授: 林俊成
Lin, Chun-Cheng
口試委員: 吳東昆
Wu, Tung-Kung
王聖凱
Wang, Sheng-Kai
林俊成
Lin, Chun-Cheng
學位類別: 碩士
Master
系所名稱: 理學院 - 化學系
Department of Chemistry
論文出版年: 2015
畢業學年度: 103
語文別: 中文
論文頁數: 130
中文關鍵詞: 酵素唾液酸
外文關鍵詞: globo
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  • 研究指出 DSGb5 和 SSEA4 為腫瘤相關抗原,Globo 系列的唾液酸化醣苷神經鞘脂可能為參與生理活動的重要抗原標記。除此之外,自然界中唾液酸通常被修飾於醣體末端。唾液酸化醣體在多樣化的生理活動中扮演關鍵的角色。唾液酸免疫球蛋白凝集素對不同的含唾液酸基配體,擁有不同的專一性辨識位。特定的鎖鑰辨識可刺激或抑制免疫訊號。近年研究顯示唾液酸免疫球蛋白凝集素或許能視為治療對象。此外,合成的醣配體已被證實為一有價值的工具,能用來解釋唾液酸免疫球蛋白凝集素與配體間的交互作用與疾病的關係。
    由於酵素合成的高度立體位向選擇性,以酵素為催化劑的研究,於醣體合成領域快速發展成具前景性的方法。本論文中,使用來自嗜血流感桿菌的醣基轉移酶 LgtD,以及大腸桿菌的尿苷轉移酶 GlmU 做為建構 globo 醣體的關鍵酵素。為了合成複雜唾液酸基化碳水化合物,我們組合 LgtD、GlmU 以及其他8種酵素,包括醣激酶、尿苷轉移酶、醣基轉移酶、唾液酸轉移酶。藉由使用不同來源的唾液酸轉移酶,成功建立唾液酸基化 globo 醣體分子庫,其中包含:α-2,3-sialyl-Gb3, α-2,6-sialyl-Gb3, α-2,3-sialyl-Gb4 以及 α-2,6-sialyl-Gb4。這些分子可作為起始物,供進一步碳水化合物生物活性之研究。


    Studies indicate DSGb5 and SSEA4 are tumor associated antigens. Globo-series ganglioside may be important epitopes involving in biological events. In addition, sialic acids are usually decorated at the terminal position of glycan chain in nature. It is not surprising that sialosides play critical roles in diverse biological process. Sialic acid-binding Ig-like lectins (Siglecs) possess different specific recognition sites to different sialic acid containing ligands. Specific lock-and-key recognition can stimulate or inhibit immunnal signals. Recent studies have showned Siglecs may serve as therapic candidates. Furthermore, it is proven that synthetic glycan ligands are valuable tools for elucidating relationship between siglec-ligand interaction and disease.
    Due to the high regio- and stereo-selectivity of enzymatic synthesis, researches of enzymes as catalysts have grown rapidily and becomed promising methods in oligosaccharide synthesis. In this thesis, glycosyltransferase (LgtD from Haemophilus influenzae) and uridyltransferase (GlmU from E. coli) were chosen as key enzymes and used to construct globoside. We assembled LgtD, GlmU and the other 8 kinds of enzymes, including kinase, uridyltransferase, glycosyltransferase, and sialyltransferase for complicated sialylated carbohydrate synthesis. A globo-sialoside library, α-2,3-sialyl-Gb3, α-2,6-sialyl-Gb3, α-2,3-sialyl-Gb4 and α-2,6-sialyl-Gb4, was successfully establish by using different source of sialyltransferases. These molecules can serve as starting materials for further carbohydrate bioactivity researches.

    目錄 謝誌 I 中文摘要 III Abstract IV 圖目錄 IX 表目錄 XII 縮寫表 XIII 酵素名稱中英對照表 XV 第一章 緒論 1 1.1 醣類的合成重要性與發展困境 1 1.2 腫瘤相關醣體抗原 4 1.2.1 乳癌相關醣體抗原 8 1.2.2 腎細胞癌相關醣類抗原 9 1.3 母乳寡醣 12 1.4 唾液酸 15 1.5 醣基轉移酶及醣核苷酸 16 1.5.1 醣激酶 (GalK, NahK) 20 1.5.2 磷酸醣核苷轉移酶 20 1.5.2.1 尿苷轉移酶 (AtUSP, GlmU) 21 1.5.2.2 胞苷合成酶 (CSS) 22 1.5.3 醣基轉移酶 (LgtC, LgtD) 23 1.5.4 唾液酸轉移酶 (PmST1, Pd26ST, CSTI) 24 1.6 磷酸-N-乙醯葡萄糖胺尿苷轉移酶 28 1.7 β-1,3-N-乙醯半乳糖胺/β-1,3-半乳糖轉移酶 31 1.8 唾液酸免疫球蛋白凝集素 32 1.9 實驗目的與動機 36 第二章 實驗結果與討論 38 2.1 以大腸桿菌誘導表現目標蛋白 38 2.1.1 建構含目標基因之重組載體 38 2.1.1.1 IMPACTTM 系統 40 2.1.1.2 pET 系統 41 2.1.2 目標基因寡核苷酸引子之設計 42 2.1.2.1 GlmU 寡核苷酸引子設計 42 2.1.2.2 LgtD 寡核苷酸引子設計 42 2.1.3 誘導目標基因之蛋白產物表現 43 2.1.3.1 GlmU 43 2.1.3.2 LgtD 44 2.2 E. col. K12 磷酸-N-乙醯葡萄糖胺尿苷轉移酶 (GlmU) 之酵素表達 45 2.3 Haemophilus influenzae RD KW20 β-1,3-N-乙醯半乳糖胺/β-1,3-半乳糖轉移酶 (LgtD) 之酵素表達 47 2.4 酵素系統應用 55 2.4.1 以 NahK 大量製備1-磷酸-N-乙醯半乳糖胺 (GalNAc-1-P) 55 2.4.2 以 GlmU製備尿苷二磷酸-N-乙醯半乳糖胺 (UDP-GalNAc) 56 2.4.3 以 GalK 大量製備1-磷酸半乳糖 (Gal-1-P) 57 2.4.4 以 AtUSP 大量製備尿苷二磷酸半乳糖 (UDP-Gal) 57 2.4.5 一鍋化製備 Gb3-C6H12N3 59 2.4.6 製備 Gb4-C6H12N3 60 2.4.7 製備 Gb5-C6H12N3 60 2.4.8 α-2,6-唾液酸基化 Globo 醣體一鍋化合成 63 2.4.9 α-2,3-唾液酸基化 Globo 醣體一鍋化合成 65 2.4.10 唾液酸化多醣體之光譜分析 67 2.4.11 結論 71 第三章 未來展望 72 第四章 實驗材料與方法 73 4.1 Material 73 4.1.1 Chemicals 73 4.1.2 Machines 73 4.1.3 Enzymes 74 4.1.4 E. coli 74 4.1.5 Vectors 75 4.1.6 The gene source of UDP-GlcNAc pyrophosphorylase 75 4.1.7 The gene source of β-1,3-galactosyltransferase / β-1,3-N- acetylgalactosaminyltransferase 75 4.2 Cloning, Overexpression, and Purification of Target Enzymes 75 4.2.1 Cloning, Overexpression, and Purification of UDP-GlcNAc pyrophosphorylase from E. coli K12 75 4.2.2 Cloning, Overexpression and Purification of β-1,3-GalNAcT / β-1,3-GalT from Haemophilus influenzae Rd KW20 77 4.3 Experiment of Enzymatic Synthesis 79 第五章 參考文獻 97

    1. (a) Schmid, A.; Dordick, J. S.; Hauer, B.; Kiener, A.; Wubbolts, M.; Witholt, B., Industrial biocatalysis today and tomorrow. Nature 2001, 409, 258-268; (b) Schoemaker, H. E.; Mink, D.; Wubbolts, M. G., Dispelling the Myths--Biocatalysis in Industrial Synthesis. Science 2003, 299, 1694-1697.
    2. Wong, S. Y. C.; Arsequell, G. Immunobiology of Carbohydrates. 1 ed.; Kluwer Academic/Plenum: New York, 2003.
    3. Fuster, M. M.; Esko, J. D., The sweet and sour of cancer: glycans as novel therapeutic targets. Nat. Rev. Cancer 2005, 5, 526-542.
    4. Carrilho, C.; Cantel, M.; Gouveia, P.; David, L., Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix. Virchows Arch. 2000, 437, 173-179.
    5. Linden, S. K.; Sutton, P.; Karlsson, N. G.; Korolik, V.; McGuckin, M. A., Mucins in the mucosal barrier to infection. Mucosal immunology 2008, 1, 183-97.
    6. Varki, A.; Cummings, R. D.; Esko, J. D.; Freeze, H. H.; Stanley, P.; Bertozzi, C. R.; Hart, G. W.; Etzler, M. E. Essentials of Glycobiology. 2 ed.; Cold Spring Harbor Laboratory: New York, 2009.
    7. Heimburg-Molinaro, J.; Lum, M.; Vijay, G.; Jain, M.; Almogren, A.; Rittenhouse-Olson, K., Cancer vaccines and carbohydrate epitopes. Vaccine 2011, 29, 8802-8826.
    8. Coley, W. B., The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am. J. Med. Sci. 1893, 105, 487-511.
    9. Wang, Q.; Ekanayaka, S. A.; Wu, J.; Zhang, J.; Guo, Z., Synthetic and Immunological Studies of 5'-N-Phenylacetyl sTn to Develop Carbohydrate-Based Cancer Vaccines and to Explore the Impacts of Linkage between Carbohydrate Antigens and Carrier Proteins. Bioconjugate Chem. 2008, 19, 2060-2067.
    10. Huang, Y.-L.; Hung, J.-T.; Cheung, S. K. C.; Lee, H.-Y.; Chu, K.-C.; Li, S.-T.; Lin, Y.-C.; Ren, C.-T.; Cheng, T.-J. R.; Hsu, T.-L.; Yu, A. L.; Wu, C.-Y.; Wong, C.-H., Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer. Proc. Natl. Acad. Sci. 2013, 110, 2517-2522.
    11. (a) Jennings, H. J.; Roy, R.; Gamian, A., Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine. J. Immunol. 1986, 137, 1708-1713; (b) Pan, Y.; Chefalo, P.; Nagy, N.; Harding, C.; Guo, Z., Synthesis and Immunological Properties of N-Modified GM3 Antigens as Therapeutic Cancer Vaccines. J. Med. Chem. 2005, 48, 875-883; (c) Yang, F.; Zheng, X.-J.; Huo, C.-X.; Wang, Y.; Zhang, Y.; Ye, X.-S., Enhancement of the Immunogenicity of Synthetic Carbohydrate Vaccines by Chemical Modifications of STn Antigen. ACS Chem. Biol. 2011, 6, 252-259.
    12. Ragupathi, G.; Koide, F.; Livingston, P. O.; Cho, Y. S.; Endo, A.; Wan, Q.; Spassova, M. K.; Keding, S. J.; Allen, J.; Ouerfelli, O.; Wilson, R. M.; Danishefsky, S. J., Preparation and Evaluation of Unimolecular Pentavalent and Hexavalent Antigenic Constructs Targeting Prostate and Breast Cancer:  A Synthetic Route to Anticancer Vaccine Candidates. J. Am. Chem. Soc. 2006, 128, 2715-2725.
    13. Berti, F.; Adamo, R., Recent Mechanistic Insights on Glycoconjugate Vaccines and Future Perspectives. ACS Chem. Biol. 2013, 8, 1653-1663.
    14. Kannagi, R.; Levery, S. B.; Ishigami, F.; Hakomori, S.; Shevinsky, L. H.; Knowles, B. B.; Solter, D., New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen, stage-specific embryonic antigen 3. J. Biol. Chem. 1983, 258, 8934-8942.
    15. (a) Chang, W.-W.; Lee, C. H.; Lee, P.; Lin, J.; Hsu, C.-W.; Hung, J.-T.; Lin, J.-J.; Yu, J.-C.; Shao, L.-e.; Yu, J.; Wong, C.-H.; Yu, A. L., Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis. Proc. Natl. Acad. Sci. 2008, 105, 11667-11672; (b) Tsai, T.-I.; Lee, H.-Y.; Chang, S.-H.; Wang, C.-H.; Tu, Y.-C.; Lin, Y.-C.; Hwang, D.-R.; Wu, C.-Y.; Wong, C.-H., Effective Sugar Nucleotide Regeneration for the Large-Scale Enzymatic Synthesis of Globo H and SSEA4. J. Am. Chem. Soc. 2013, 135, 14831-14839.
    16. Lee, H.-Y.; Chen, C.-Y.; Tsai, T.-I.; Li, S.-T.; Lin, K.-H.; Cheng, Y.-Y.; Ren, C.-T.; Cheng, T.-J. R.; Wu, C.-Y.; Wong, C.-H., Immunogenicity Study of Globo H Analogues with Modification at the Reducing or Nonreducing End of the Tumor Antigen. J. Am. Chem. Soc. 2014, 136, 16844-16853.
    17. Satoh, M.; Handa, K.; Saito, S.; Tokuyama, S.; Ito, A.; Miyao, N.; Orikasa, S.; Hakomori, S.-i., Disialosyl Galactosylgloboside as an Adhesion Molecule Expressed on Renal Cell Carcinoma and Its Relationship to Metastatic Potential. Cancer Res. 1996, 56, 1932-1938.
    18. Senda, M.; Ito, A.; Tsuchida, A.; Hagiwara, T.; Kaneda, T.; Nakamura, Y.; Kasama, K.; Kiso, M.; Yoshikawa, K.; Katagiri, Y.; Ono, Y.; Ogiso, M.; Urano, T.; Furukawa, K.; Oshima, S.; Furukawa, K., Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers. Biochem. J. 2007, 402, 459-470.
    19. Ito, A.; Handa, K.; Withers, D. A.; Satoh, M.; Hakomori, S.-i., Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression. FEBS Letters 2001, 498, 116-120.
    20. Kawasaki, Y.; Ito, A.; Withers, D. A.; Taima, T.; Kakoi, N.; Saito, S.; Arai, Y., Ganglioside DSGb5, preferred ligand for Siglec-7, inhibits NK cell cytotoxicity against renal cell carcinoma cells. Glycobiology 2010, 20, 1373-1379.
    21. Shimada, S.; Ito, A.; Kawasaki, Y.; Kakoi, N.; Taima, T.; Mitsuzuka, K.; Watanabe, M.; Saito, S.; Arai, Y., Ganglioside disialosyl globopentaosylceramide is an independent predictor of PSA recurrence-free survival following radical prostatectomy. Prostate Cancer Prostatic Dis. 2014, 17, 199-205.
    22. (a) Ishida, H.; Miyawaki, R.; Kiso, M.; Hasegawa, A., Synthetic Studies on Sialoglycoconjugates 82: First Total Synthesis of Sialyl Globopentaosyl Ceramide (V3Neu5AcGb5Cer) and its Positional Isomer (V6Neu5AcGb5Cer)1,2. J. Carbohydr. Chem. 1996, 15, 163-182; (b) Lassaletta, J. M.; Carlsson, K.; Garegg, P. J.; Schmidt, R. R., Total Synthesis of Sialylgalactosylgloboside:  Stage-Specific Embryonic Antigen 4. J. Org. Chem. 1996, 61, 6873-6880.
    23. Wang, Z.; Zhou, L.; El-Boubbou, K.; Ye, X.; Huang, X., Multi-Component One-Pot Synthesis of the Tumor-Associated Carbohydrate Antigen Globo-H Based on Preactivation of Thioglycosyl Donors. J. Org. Chem. 2007, 72, 6409-6420.
    24. Wang, Z.; Gilbert, M.; Eguchi, H.; Yu, H.; Cheng, J.; Muthana, S.; Zhou, L.; Wang, P. G.; Chen, X.; Huang, X., Chemoenzymatic Syntheses of Tumor-Associated Carbohydrate Antigen Globo-H and Stage-Specific Embryonic Antigen 4. Adv. Synth. Catal. 2008, 350, 1717-1728.
    25. Bode, L., Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology 2012, 22, 1147-1162.
    26. Koliwer-Brandl, H.; Siegert, N.; Umnus, K.; Kelm, A.; Tolkach, A.; Kulozik, U.; Kuballa, J.; Cartellieri, S.; Kelm, S., Lectin inhibition assays for the analysis of bioactive milk sialoglycoconjugates. Int. Dairy J. 2011, 21, 413-420.
    27. (a) Yao, W.; Yan, J.; Chen, X.; Wang, F.; Cao, H., Chemoenzymatic synthesis of lacto-N-tetrasaccharide and sialyl lacto-N-tetrasaccharides. Carbohydr. Res. 2015, 401, 5-10; (b) Yu, H.; Lau, K.; Thon, V.; Autran, C. A.; Jantscher-Krenn, E.; Xue, M.; Li, Y.; Sugiarto, G.; Qu, J.; Mu, S.; Ding, L.; Bode, L.; Chen, X., Synthetic Disialyl Hexasaccharides Protect Neonatal Rats from Necrotizing Enterocolitis. Angew. Chem. Int. Ed. 2014, 53, 6687-6691; (c) Li, L.; Liu, Y.; Li, T.; Wang, W.; Yu, Z.; Ma, C.; Qu, J.; Zhao, W.; Chen, X.; Wang, P. G., Efficient chemoenzymatic synthesis of novel galacto-N-biose derivatives and their sialylated forms. Chem. Commun. 2015, 51, 10310-10313.
    28. Kunz, C.; Rudloff, S.; Baier, W.; Klein, N.; Strobel, S., Oligosaccharides in Human Milk: Structural, Functional, and Metabolic Aspects. Annu. Rev. Nutr. 2000, 20, 699-722.
    29. Blix, F. G.; Gottschalk, A.; Klenk, E., Proposed Nomenclature in the Field of Neuraminic and Sialic Acids. Nature 1957, 179, 1088-1088.
    30. Varki, A., Diversity in the sialic acids. Glycobiology 1992, 2, 25-40.
    31. Bülter, T.; Elling, L., Enzymatic synthesis of nucleotide sugars. Glycoconj. J. 1999, 16, 147-159.
    32. Tanaka, H.; Yoshimura, Y.; Jørgensen, M. R.; Cuesta-Seijo, J. A.; Hindsgaul, O., A Simple Synthesis of Sugar Nucleoside Diphosphates by Chemical Coupling in Water. Angew. Chem. Int. Ed. 2012, 51, 11531-11534.
    33. Tsai, T.-I.; Wu, C.-Y.; Wong, C.-H., Large-Scale Enzymatic Synthesis of Glycans with Cofactor Regeneration. In Glycoscience: Biology and Medicine, Endo, T.; Seeberger, P. H.; Hart, G. W.; Wong, C.-H.; Taniguchi, N., Eds. Springer Japan: 2014; pp 1-9.
    34. (a) Cai, L.; Guan, W.; Wang, W.; Zhao, W.; Kitaoka, M.; Shen, J.; O’Neil, C.; Wang, P. G., Substrate specificity of N-acetylhexosamine kinase towards N-acetylgalactosamine derivatives. Bioorg. Med. Chem. Lett. 2009, 19, 5433-5435; (b) Cai, L.; Guan, W.; Kitaoka, M.; Shen, J.; Xia, C.; Chen, W.; Wang, P. G., A chemoenzymatic route to N-acetylglucosamine-1-phosphate analogues: substrate specificity investigations of N-acetylhexosamine 1-kinase. Chem. Commun. 2009, 2944-2946.
    35. Chen, X.; Zhang, J.; Kowal, P.; Liu, Z.; Andreana, P. R.; Lu, Y.; Wang, P. G., Transferring a Biosynthetic Cycle into a Productive Escherichia coli Strain:  Large-Scale Synthesis of Galactosides. J. Am. Chem. Soc. 2001, 123, 8866-8867.
    36. Bhatt, V. S.; Guo, C.-y.; Guan, W.; Zhao, G.; Yi, W.; Liu, Z.-j.; Wang, P. G., Altered architecture of substrate binding region defines the unique specificity of UDP-GalNAc 4-epimerases. Protein Sci. 2011, 20, 856-866.
    37. (a) Litterer, L. A.; Schnurr, J. A.; Plaisance, K. L.; Storey, K. K.; Gronwald, J. W.; Somers, D. A., Characterization and expression of Arabidopsis UDP-sugar pyrophosphorylase. Plant Physio. Biochem. 2006, 44, 171-180; (b) Liu, J.; Zou, Y.; Guan, W.; Zhai, Y.; Xue, M.; Jin, L.; Zhao, X.; Dong, J.; Wang, W.; Shen, J.; Wang, P. G.; Chen, M., Biosynthesis of nucleotide sugars by a promiscuous UDP-sugar pyrophosphorylase from Arabidopsis thaliana (AtUSP). Bioorg. Med. Chem. Lett. 2013, 23, 3764-3768; (c) Guo, Y.; Fang, J.; Li, T.; Li, X.; Ma, C.; Wang, X.; Wang, P. G.; Li, L., Comparing substrate specificity of two UDP-sugar pyrophosphorylases and efficient one-pot enzymatic synthesis of UDP-GlcA and UDP-GalA. Carbohydr. Res. 2015, 411, 1-5.
    38. Zhao, G.; Guan, W.; Cai, L.; Wang, P. G., Enzymatic route to preparative-scale synthesis of UDP-GlcNAc/GalNAc, their analogues and GDP-fucose. Nat. Protoc. 2010, 5, 636-646.
    39. Knorst, M.; Fessner, W.-D., CMP-Sialate Synthetase from Neisseria meningitidis − Overexpression and Application to the Synthesis of Oligosaccharides Containing Modified Sialic Acids. Adv. Synth. Catal. 2001, 343, 698-710.
    40. Zhang, J.; Kowal, P.; Chen, X.; George Wang, P., Large-scale synthesis of globotriose derivatives through recombinant E. coli. Org. Biomol. Chem. 2003, 1, 3048-3053.
    41. Liu, Z.; Lu, Y.; Zhang, J.; Pardee, K.; Wang, P. G., P1 Trisaccharide (Galα1,4Galβ1,4GlcNAc) Synthesis by Enzyme Glycosylation Reactions Using Recombinant Escherichia coli. Appl. Environ. Microb. 2003, 69, 2110-2115.
    42. Wakarchuk, W. W.; Cunningham, A.; Watson, D. C.; Young, N. M., Role of paired basic residues in the expression of active recombinant galactosyltransferases from the bacterial pathogen Neisseria meningitidis. Protein Eng. 1998, 11, 295-302.
    43. Randriantsoa, M.; Drouillard, S.; Breton, C.; Samain, E., Synthesis of globopentaose using a novel β1,3-galactosyltransferase activity of the Haemophilus influenzae β1,3-N-acetylgalactosaminyltransferase LgtD. FEBS Lett. 2007, 581, 2652-2656.
    44. Yu, C.-C.; Withers, S. G., Recent Developments in Enzymatic Synthesis of Modified Sialic Acid Derivatives. Adv. Synth. Catal. 2015, 357, 1633-1654.
    45. Lairson, L. L.; Henrissat, B.; Davies, G. J.; Withers, S. G., Glycosyltransferases: Structures, Functions, and Mechanisms. Annu. Rev. Biochem. 2008, 77, 521-555.
    46. Yu, H.; Chokhawala, H.; Karpel, R.; Yu, H.; Wu, B.; Zhang, J.; Zhang, Y.; Jia, Q.; Chen, X., A Multifunctional Pasteurella multocida Sialyltransferase:  A Powerful Tool for the Synthesis of Sialoside Libraries. J. Am. Chem. Soc. 2005, 127, 17618-17619.
    47. (a) Ni, L.; Chokhawala, H. A.; Cao, H.; Henning, R.; Ng, L.; Huang, S.; Yu, H.; Chen, X.; Fisher, A. J., Crystal Structures of Pasteurella multocida Sialyltransferase Complexes with Acceptor and Donor Analogues Reveal Substrate Binding Sites and Catalytic Mechanism. Biochemistry 2007, 46, 6288-6298; (b) Sugiarto, G.; Lau, K.; Qu, J.; Li, Y.; Lim, S.; Mu, S.; Ames, J. B.; Fisher, A. J.; Chen, X., A Sialyltransferase Mutant with Decreased Donor Hydrolysis and Reduced Sialidase Activities for Directly Sialylating LewisX. ACS Chem. Biol. 2012, 7, 1232-1240.
    48. Kajihara, Y.; Yamamoto, T.; Nagae, H.; Nakashizuka, M.; Sakakibara, T.; Terada, I., A Novel α-2,6-Sialyltransferase:  Transfer of Sialic Acid to Fucosyl and Sialyl Trisaccharides. J. Org. Chem. 1996, 61, 8632-8635.
    49. Cheng, J.; Huang, S.; Yu, H.; Li, Y.; Lau, K.; Chen, X., Trans-sialidase activity of Photobacterium damsela α2,6-sialyltransferase and its application in the synthesis of sialosides. Glycobiology 2010, 20, 260-268.
    50. (a) Nycholat, C. M.; Peng, W.; McBride, R.; Antonopoulos, A.; de Vries, R. P.; Polonskaya, Z.; Finn, M. G.; Dell, A.; Haslam, S. M.; Paulson, J. C., Synthesis of biologically active N- and O-linked glycans with multisialylated poly-N-acetyllactosamine extensions using P. damsela alpha2-6 sialyltransferase. J. Am. Chem. Soc. 2013, 135, 18280-3; (b) Teo, C.-F.; Hwang, T.-S.; Chen, P.-H.; Hung, C.-H.; Gao, H.-S.; Chang, L.-S.; Lin, C.-H., Synthesis of Sialyl TN Glycopeptides – Enzymatic Sialylation by α2,6-Sialyltransferase from Photobacterium damsela. Adv. Synth. Catal. 2005, 347, 967-972; (c) Yu, H.; Huang, S.; Chokhawala, H.; Sun, M.; Zheng, H.; Chen, X., Highly Efficient Chemoenzymatic Synthesis of Naturally Occurring and Non-Natural α-2,6-Linked Sialosides: A P. damsela α-2,6-Sialyltransferase with Extremely Flexible Donor–Substrate Specificity. Angew. Chem. Int. Ed. 2006, 45, 3938-3944; (d) Meng, X.; Yao, W.; Cheng, J.; Zhang, X.; Jin, L.; Yu, H.; Chen, X.; Wang, F.; Cao, H., Regioselective chemoenzymatic synthesis of ganglioside disialyl tetrasaccharide epitopes. J. Am. Chem. Soc. 2014, 136, 5205-8.
    51. Chiu, C. P. C.; Lairson, L. L.; Gilbert, M.; Wakarchuk, W. W.; Withers, S. G.; Strynadka, N. C. J., Structural Analysis of the α-2,3-Sialyltransferase Cst-I from Campylobacter jejuni in Apo and Substrate-Analogue Bound Forms. Biochemistry 2007, 46, 7196-7204.
    52. Mengin-Lecreulx, D.; van Heijenoort, J., Identification of the glmU gene encoding N-acetylglucosamine-1-phosphate uridyltransferase in Escherichia coli. J. Bacteriol. 1993, 175, 6150-6157.
    53. Walker, J. E.; Gay, N. J.; Saraste, M.; Eberle, A. N., DNA sequence around the Escherichia coli unc operon. Completion of the sequence of a 17 kilobase segment containing asnA, oriC, unc, glmS and phoS. Biochem. J. 1984, 224, 799-815.
    54. (a) Mengin-Lecreulx, D.; van Heijenoort, J., Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis. J. Bacteriol. 1994, 176, 5788-5795; (b) De Luca, C. L., Manfred; Crescenzi, F.; Martini, I.; Shen, G.-J.; O'Regan, M.; Wong, C.-H., Overexpression, one-step purification and characterization of UDP-glucose dehydrogenase and UDP-N-acetylglucosamine pyrophosphorylase. Bioorg. Med. Chem. 1996, 4, 131-141.
    55. Bourgeaux, V.; Piller, F.; Piller, V., Two-step enzymatic synthesis of UDP-N-acetylgalactosamine. Bioorg. Med. Chem. Lett. 2005, 15, 5459-5462.
    56. Fleischmann, R. D.; Adams, M. D.; White, O.; Clayton, R. A.; Kirkness, E. F.; Kerlavage, A. R.; Bult, C. J.; Tomb, J. F.; Dougherty, B. A.; Merrick, J. M.; al., e., Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 1995, 269, 496-512.
    57. (a) Kimura, A.; Hansen, E. J., Antigenic and phenotypic variations of Haemophilus influenzae type b lipopolysaccharide and their relationship to virulence. Infect. Immun. 1986, 51, 69-79; (b) Hood, D. W.; Deadman, M. E.; Allen, T.; Masoud, H.; Martin, A.; Brisson, J. R.; Fleischmann, R.; Venter, J. C.; Richards, J. C.; Moxon, E. R., Use of the complete genome sequence information of Haemophilus influenzae strain Rd to investigate lipopolysaccharide biosynthesis. Mol. Microbiol. 1996, 22, 951-965; (c) Risberg, A.; Masoud, H.; Martin, A.; Richards, J. C.; Moxon, E. R.; Schweda, E. K. H., Structural analysis of the lipopolysaccharide oligosaccharide epitopes expressed by a capsule-deficient strain of Haemophilus influenzae Rd. Eur. J. Biochem. 1999, 261, 171-180.
    58. Shao, J.; Zhang, J.; Kowal, P.; Lu, Y.; George Wang, P., Overexpression and biochemical characterization of β-1,3-N-acetylgalactosaminyltransferase LgtD from Haemophilus influenzae strain Rd. Biochem. Biophys. Res. Commun. 2002, 295, 1-8.
    59. (a) Shao, J.; Zhang, J.; Kowal, P.; Wang, P. G., Donor Substrate Regeneration for Efficient Synthesis of Globotetraose and Isoglobotetraose. Appl. Environ. Microb. 2002, 68, 5634-5640; (b) Shao, J.; Zhang, J.; Kowal, P.; Lu, Y.; Wang, P. G., Efficient synthesis of globoside and isogloboside tetrasaccharides by using beta-1,3-N-acetylgalactosaminyltransferase / UDP-N-acetylglucosamine C4 epimerase fusion protein. Chem. Commun. 2003, 1422-1423.
    60. Antoine, T.; Bosso, C.; Heyraud, A.; Samain, E., Large scale in vivo synthesis of globotriose and globotetraose by high cell density culture of metabolically engineered Escherichia coli. Biochimie 2005, 87, 197-203.
    61. Corfield, A. P., Mucins: A biologically relevant glycan barrier in mucosal protection. Biochimi. Biophys. Acta, Gen. Subj. 2015, 1850, 236-252.
    62. Crocker, P. R.; Paulson, J. C.; Varki, A., Siglecs and their roles in the immune system. Nat. Rev. Immunol. 2007, 7, 255-266.
    63. Jiang, T.; Yu, J.-T.; Hu, N.; Tan, M.-S.; Zhu, X.-C.; Tan, L., CD33 in Alzheimer's Disease. Mol. Neurobiol. 2014, 49, 529-535.
    64. Rillahan, C. D.; Macauley, M. S.; Schwartz, E.; He, Y.; McBride, R.; Arlian, B. M.; Rangarajan, J.; Fokin, V. V.; Paulson, J. C., Disubstituted sialic acid ligands targeting siglecs CD33 and CD22 associated with myeloid leukaemias and B cell lymphomas. Chem. Sci. 2014, 5, 2398-2406.
    65. Macauley, M. S.; Crocker, P. R.; Paulson, J. C., Siglec-mediated regulation of immune cell function in disease. Nat. Rev. Immunol. 2014, 14, 653-666.
    66. Robert Novy, B. M. Use of glucose to control basal expression in the pET System.
    67. 簡薇庭. Sequencial Enzymatic Synthesis of Sugar Nucleotides and Its Application on Poly-LacNAc Synthesis. 博士論文, 國立清華大學, 2012.
    68. 李泗芃. Kinetics Studies with Galactokinase from Meiothermus taiwanensis ATCC BAA-400 and Application of Galactokinase to Synthesize Pk antigen. 碩士論文, 國立清華大學, 2012.
    69. 游景晴. Site-Specific CMP-Sialic Acid Synthetase Immobilized Magnetic Nanoparticle and Its Application in Organic Synthesis. 碩士論文, 國立清華大學, 2007.
    70. 游景晴. Development of Nanoparticle-based System for Enzyme Immobilization and High Through-put Enzyme Screening. 博士論文, 國立清華大學, 2012.
    71. Su, D. M.; Eguchi, H.; Yi, W.; Li, L.; Wang, P. G.; Xia, C., Enzymatic Synthesis of Tumor-Associated Carbohydrate Antigen Globo-H Hexasaccharide. Org. Lett. 2008, 10, 1009-1012.
    72. Guan, W.; Cai, L.; Fang, J.; Wu, B.; George Wang, P., Enzymatic synthesis of UDP-GlcNAc/UDP-GalNAc analogs using N-acetylglucosamine 1-phosphate uridyltransferase (GlmU). Chem. Commun. 2009, 6976-6978.
    73. Li, S.-P.; Hsiao, W.-C.; Yu, C.-C.; Chien, W.-T.; Lin, H.-J.; Huang, L.-D.; Lin, C.-H.; Wu, W.-L.; Wu, S.-H.; Lin, C.-C., Characterization of Meiothermus taiwanensis Galactokinase and its Use in the One-Pot Enzymatic Synthesis of Uridine Diphosphate-Galactose and the Chemoenzymatic Synthesis of the Carbohydrate Antigen Stage Specific Embryonic Antigen-3. Adv. Synth. Catal. 2014, 356, 3199-3213.

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