請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16393完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林俊宏(Chung-Hung Lin) | |
| dc.contributor.author | Yu-Nong Lin | en |
| dc.contributor.author | 林宥穠 | zh_TW |
| dc.date.accessioned | 2021-06-07T18:12:48Z | - |
| dc.date.copyright | 2012-07-16 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-06-25 | |
| dc.identifier.citation | Appelmelk, B.J., Negrini, R., Moran, A.P., and Kuipers, E.J. (1997). Molecular mimicry between Helicobacter pylori and the host. Trends Microbiol. 5, 70-73.
Arjona, O., Gomez, A.M., Lopez, J.C., and Plumet, J. (2007). Synthesis and conformational and biological aspects of carbasugars. Chem. Rev. 107, 1919-2036. Avent, N.D. (1997). Human erythrocyte antigen expression: its molecular bases. Br. J. Biomed. Sci. 54, 16-37. Barthel, S.R., Gavino, J.D., Wiese, G.K., Jaynes, J.M., Siddiqui, J., and Dimitroff, C.J. (2008). Analysis of glycosyltransferase expression in metastatic prostate cancer cells capable of rolling activity on microvascular endothelial (E)-selectin. Glycobiology 18, 806-817. Barthel, S.R., Wiese, G.K., Cho, J., Opperman, M.J., Hays, D.L., Siddiqui, J., Pienta, K.J., Furie, B., and Dimitroff, C.J. (2009). Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking. Proc. Natl. Acad. Sci. USA 106, 19491-19496. Becker, D.J., and Lowe, J.B. (2003). Fucose: biosynthesis and biological function in mammals. Glycobiology 13, 41R-53R. Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., and Karplus, M. (2004). CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. Comput. Chem. 4, 187-217. Bryan, M.C., Lee, L.V., and Wong, C.H. (2004). High-throughput identification of fucosyltransferase inhibitors using carbohydrate microarrays. Bioorg. Med. Chem. Lett. 14, 3185-3188. Brzezinski, K., Stepkowski, T., Panjikar, S., Bujacz, G., and Jaskolski, M. (2007). High-resolution structure of NodZ fucosyltransferase involved in the biosynthesis of the nodulation factor. Acta Biochim. Pol. 54, 537-549. Bulter, T., and Elling, L. (1999). Enzymatic synthesis of nucleotide sugars. Glycoconj. J. 16, 147-159. Burkart, M.D., Vincent, S.P., Duffels, A., Murray, B.W., Ley, S.V., and Wong, C.H. (2000). Chemo-enzymatic synthesis of fluorinated sugar nucleotide: useful mechanistic probes for glycosyltransferases. Bioorg. Med. Chem. 8, 1937-1946. Byun, S.G., Kim, M.D., Lee, W.H., Lee, K.J., Han, N.S., and Seo, J.H. (2007). Production of GDP-L-fucose, L-fucose donor for fucosyloligosaccharide synthesis, in recombinant Escherichia coli. Appl. Microbiol. Biotechnol. 74, 768-775. Chang, C.F., Ho, C.W., Wu, C.Y., Chao, T.A., Wong, C.H., and Lin, C.H. (2004). Discovery of picomolar slow tight-binding inhibitors of alpha-fucosidase. Chem. Biol. 11, 1301-1306. Coyne, M.J., Reinap, B., Lee, M.M., and Comstock, L.E. (2005). Human symbionts use a host-like pathway for surface fucosylation. Science 307, 1778-1781. de Vries, T., Knegtel, R.M., Holmes, E.H., and Macher, B.A. (2001). Fucosyltransferases: structure/function studies. Glycobiology 11, 119R-128R. Doig, P., Paranchych, W., Sastry, P.A., and Irvin, R.T. (1989). Human buccal epithelial cell receptors of Pseudomonas aeruginosa: identification of glycoproteins with pilus binding activity. Can. J. Microbiol. 35, 1141-1145. Dube, D.H., and Bertozzi, C.R. (2005). Glycans in cancer and inflammation--potential for therapeutics and diagnostics. Nat. Rev. Drug Discov. 4, 477-488. Dupuy, F., Petit, J.M., Mollicone, R., Oriol, R., Julien, R., and Maftah, A. (1999). A single amino acid in the hypervariable stem domain of vertebrate alpha1,3/1,4-fucosyltransferases determines the type 1/type 2 transfer. Characterization of acceptor substrate specificity of the lewis enzyme by site-directed mutagenesis. J. Biol. Chem. 274, 12257-12262. Ge, Z., Chan, N.W., Palcic, M.M., and Taylor, D.E. (1997). Cloning and heterologous expression of an alpha1,3-fucosyltransferase gene from the gastric pathogen Helicobacter pylori. J. Biol. Chem. 272, 21357-21363. Gilbert, M., Cunningham, A.M., Watson, D.C., Martin, A., Richards, J.C., and Wakarchuk, W.W. (1997). Characterization of a recombinant Neisseria meningitidis alpha-2,3-sialyltransferase and its acceptor specificity. Eur. J. Biochem. 249, 187-194. Ginsburg, V. (1960). Formation of guanosine diphosphate L-fucose from guanosine diphosphate D-mannose. J. Biol. Chem. 235, 2196-2201. Glick, M.C., Kothari, V.A., Liu, A., Stoykova, L.I., and Scanlin, T.F. (2001). Activity of fucosyltransferases and altered glycosylation in cystic fibrosis airway epithelial cells. Biochimie 83, 743-747. Gonzalo, P., Sontag, B., Guillot, D., and Reboud, J.P. (1995). Fluorometric assay of GTPase activity: application to the couple elongation factor eEF-2-ribosome. Anal. Biochem. 225, 178-180. Guo, Q., Guo, B., Wang, Y., Wu, J., Jiang, W., Zhao, S., Qiao, S., and Wu, Y. (2012). Functional analysis of alpha1,3/4-fucosyltransferase VI in human hepatocellular carcinoma cells. Biochem. Biophys. Res. Commun. 417, 311-317. Hanninen, A., Taylor, C., Streeter, P.R., Stark, L.S., Sarte, J.M., Shizuru, J.A., Simell, O., and Michie, S.A. (1993). Vascular addressins are induced on islet vessels during insulitis in nonobese diabetic mice and are involved in lymphoid cell binding to islet endothelium. J. Clin. Invest. 92, 2509-2515. Ho, C.W., Lin, Y.N., Chang, C.F., Li, S.T., Wu, Y.T., Wu, C.Y., Liu, S.W., Li, Y.K., and Lin, C.H. (2006). Discovery of different types of inhibition between the human and thermotoga maritima alpha-fucosidases by fuconojirimycin-based derivatives. Biochemistry 45, 5695-5702. Ho, C.W., Popat, S.D., Liu, T.W., Tsai, K.C., Ho, M.J., Chen, W.H., Yang, A.S., and Lin, C.H. (2010). Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors. ACS Chem. Biol. 5, 489-497. Hosoguchi, K., Maeda, T., Furukawa, J., Shinohara, Y., Hinou, H., Sekiguchi, M., Togame, H., Takemoto, H., Kondo, H., and Nishimura, S. (2010). An efficient approach to the discovery of potent inhibitors against glycosyltransferases. J. Med. Chem. 53, 5607-5619. Ichikawa, Y., Lin, Y.C., Dumas, D.P., Shen, G.J., Garcia-Junceda, E., Williams, M.A., Bayer, R., Ketcham, C., Walker, L.E., Paulson, J.C., Wong, C.H. (1992a). Chemical-enzymatic synthesis and conformational-analysis of sialyl Lewis-X and derivatives. J. Am. Chem. Soc. 114, 9283-9298. Ichikawa, Y., Sim, M.M., and Wong, C.H. (1992b). Efficient chemical synthesis of GDP-fucose. J. Org. Chem. 57, 2943-2946. Ihara, H., Ikeda, Y., Toma, S., Wang, X., Suzuki, T., Gu, J., Miyoshi, E., Tsukihara, T., Honke, K., Matsumoto, A., Nakagawa, A., Taniguchi, N. (2007). Crystal structure of mammalian alpha1,6-fucosyltransferase, FUT8. Glycobiology 17, 455-466. Ishihara, H., and Heath, E.C. (1968). The metabolism of L-fucose. IV. The biosynthesis of guanosine diphosphate L-fucose in porcine liver. J. Biol. Chem. 243, 1110-1115. Ishihara, H., Massaro, D.J., and Heath, E.C. (1968). The metabolism of L-fucose. 3. The enzymatic synthesis of beta-L-fucose 1-phosphate. J. Biol. Chem. 243, 1103-1109. Izumi, M., Kaneko, S., Yuasa, H., and Hashimoto, H. (2006). Synthesis of bisubstrate analogues targeting alpha-1,3-fucosyltransferase and their activities. Org. Biomol. Chem. 4, 681-690. Kamińska, J., Dziecioł, J., and Kościelak, J. (1999). Triazine dyes as inhibitors and affinity ligands of glycosyltransferases. Glycoconj. J. 16, 719-723. Karwaski, M.F., Wakarchuk, W.W., and Gilbert, M. (2002). High-level expression of recombinant Neisseria CMP-sialic acid synthetase in Escherichia coli. Protein Expr. Purif. 25, 237-240. Kelley, L.A., and Sternberg, M.J. (2009). Protein structure prediction on the Web: a case study using the Phyre server. Nat. Protoc. 4, 363-371. Koizumi, S., Endo, T., Tabata, K., Nagano, H., and Ohnishi, J. (2000). Large-scale production of GDP-fucose and Lewis X by bacterial coupling. J. Ind. Microbiol. Biotechnol. 25, 213-217. Kotake, T., Hojo, S., Tajima, N., Matsuoka, K., Koyama, T., and Tsumuraya, Y. (2008). A bifunctional enzyme with L-fucokinase and GDP-L-fucose pyrophosphorylase activities salvages free L-fucose in Arabidopsis. J. Biol. Chem. 283, 8125-8135. Larkin, M., Ahern, T.J., Stoll, M.S., Shaffer, M., Sako, D., O'Brien, J., Yuen, C.T., Lawson, A.M., Childs, R.A., Barone, K.M., Langer-Saferll, P.R., Hasegawa, A., Kiso, M., Larsenll, G.R. and Feizi, T. (1992). Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the endothelial-leukocyte adhesion molecule E-selectin. Dependence of the carbohydrate binding activity on E-selectin density. J. Biol. Chem. 267, 13661-13668. Lee, L.V., Mitchell, M.L., Huang, S.J., Fokin, V.V., Sharpless, K.B., and Wong, C.H. (2003). A potent and highly selective inhibitor of human alpha-1,3-fucosyltransferase via click chemistry. J. Am. Chem. Soc. 125, 9588-9589. Legaigneur, P., Breton, C., El Battari, A., Guillemot, J.C., Auge, C., Malissard, M., Berger, E.G., and Ronin, C. (2001). Exploring the acceptor substrate recognition of the human beta-galactoside alpha 2,6-sialyltransferase. J. Biol. Chem. 276, 21608-21617. Liao, T.H., and Barber, G.A. (1971). The synthesis of guanosine 5'-diphosphate-L-fucose by enzymes of a higher plant. Biochim. Biophys. Acta 230, 64-71. Lin, T., Chang, W., Chen, C., and Tsai, Y. (2005). Stachybotrydial, a potent inhibitor of fucosyltransferase and sialyltransferase. Biochem. Biophys. Res. Comm. 331, 953-957. Listinsky, J.J., Listinsky, C.M., Alapati, V., and Siegal, G.P. (2001). Cell surface fucose ablation as a therapeutic strategy for malignant neoplasms. Adv. Anat. Pathol. 8, 330-337. Liu, T.W., Ito, H., Chiba, Y., Kubota, T., Sato, T., and Narimatsu, H. (2011). Functional expression of L-fucokinase/guanosine 5'-diphosphate-L-fucose pyrophosphorylase from Bacteroides fragilis in Saccharomyces cerevisiae for the production of nucleotide sugars from exogenous monosaccharides. Glycobiology 21, 1228-1236. Lowe, J.B., Stoolman, L.M., Nair, R.P., Larsen, R.D., Behrend, T.L., and Marks, R.M. (1991). A transfected human fucosyltransferase cDNA determines biosynthesis of oligosaccharide ligand(s) for endothelial-leukocyte adhesion molecule I. Biochem. Soc. Trans. 19, 649-653. Luengo, J.I., and Gleason, J.G. (1992). Synthesis of C-fucopyranosyl analogs of GDP-L-fucose as inhibitors of fucosyltransferases. Tetrahedron Lett. 33, 6911-6914. Luo, Y., Koles, K., Vorndam, W., Haltiwanger, R.S., and Panin, V.M. (2006). Protein O-fucosyltransferase 2 adds O-fucose to thrombospondin type 1 repeats. J. Biol. Chem. 281, 9393-9399. Ma, B., Simala-Grant, J.L., and Taylor, D.E. (2006). Fucosylation in prokaryotes and eukaryotes. Glycobiology 16, 158R-184R. Maeda, T., and Nishimura, S. (2008). FRET-based direct and continuous monitoring of human fucosyltransferases activity: an efficient synthesis of versatile GDP-L-fucose derivatives from abundant D-galactose. Eur. J. Chem. 14, 478-487. Marques Jr, E.T., Jr., Ichikawa, Y., Strand, M., August, J.T., Hart, G.W., and Schnaar, R.L. (2001). Fucosyltransferases in Schistosoma mansoni development. Glycobiology 11, 249-259. Martin-Satue, M., de Castellarnau, C., and Blanco, J. (1999). Overexpression of alpha(1,3)-fucosyltransferase VII is sufficient for the acquisition of lung colonization phenotype in human lung adenocarcinoma HAL-24Luc cells. Br. J. Cancer 80, 1169-1174. Mas, E., Pasqualini, E., Caillol, N., El Battari, A., Crotte, C., Lombardo, D., and Sadoulet, M.O. (1998). Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines. Glycobiology 8, 605-613. Michie, S.A., Streeter, P.R., Bolt, P.A., Butcher, E.C., and Picker, L.J. (1993). The human peripheral lymph node vascular addressin. An inducible endothelial antigen involved in lymphocyte homing. Am. J. Pathol. 143, 1688-1698. Mitchell, M.L., Tian, F., Lee, L.V., and Wong, C.H. (2002). Synthesis and evaluation of transition-state analogue inhibitors of alpha-1,3-fucosyltransferase. Angew. Chem. Int. Ed. Engl. 41, 3041-3044. Mollicone, R., Cailleau, A., and Oriol, R. (1995). Molecular genetics of H, Se, Lewis and other fucosyltransferase genes. Transfus. Clin. Biol. 2, 235-242. Mollicone, R., Gibaud, A., Francois, A., Ratcliffe, M., and Oriol, R. (1990). Acceptor specificity and tissue distribution of three human alpha-3-fucosyltransferases. Eur. J. Biochem. 191, 169-176. Mong, T.K., Lee, L.V., Brown, J., Esko, J., and Wong, C.H. (2003). Synthesis of N-acetyllactosamine derivatives with variation in the aglycon moiety for the study of inhibition of sialyl Lewis x expression. Chem. Bio. Chem. 4, 835-840. Muller, B., Schaub, C., and Schmidt, R.R. (1998). Efficient Sialyltransferase Inhibitors Based on Transition-State Analogues of the Sialyl Donor. Angew. Chem. Int. Ed. 37, 2893–2897. Niu, X., Fan, X., Sun, J., Ting, P., Narula, S., and Lundell, D. (2004). Inhibition of fucosyltransferase VII by gallic acid and its derivatives. Arch. Biochem. Biophys. 425, 51-57. Noda, K., Miyoshi, E., Uozumi, N., Yanagidani, S., Ikeda, Y., Gao, C., Suzuki, K., Yoshihara, H., Yoshikawa, K., Kawano, K., Hayashi, N., Hori, M., Taniguchi, N. (1998). Gene expression of alpha1-6 fucosyltransferase in human hepatoma tissues: a possible implication for increased fucosylation of alpha-fetoprotein. Hepatology 28, 944-952. Norris, A., Whitelegge, J., Strouse, M.J., Faull, K., and Toyokuni, T. (2004). Inhibition kinetics of carba- and C-fucosyl analogues of GDP-fucose against fucosyltransferase V: implication for the reaction mechanism. Bioorg. Med. Chem. Lett. 14, 571-573. Ogawa, J., Inoue, H., and Koide, S. (1996). Expression of alpha-1,3-fucosyltransferase type IV and VII genes is related to poor prognosis in lung cancer. Cancer Res. 56, 325-329. Okazaki, A., Shoji-Hosaka, E., Nakamura, K., Wakitani, M., Uchida, K., Kakita, S., Tsumoto, K., Kumagai, I., and Shitara, K. (2004). Fucose depletion from human IgG1 oligosaccharide enhances binding enthalpy and association rate between IgG1 and FcgammaRIIIa. J. Mol. Biol. 336, 1239-1249. Oriol, R., Mollicone, R., Cailleau, A., Balanzino, L., and Breton, C. (1999). Divergent evolution of fucosyltransferase genes from vertebrates, invertebrates, and bacteria. Glycobiology 9, 323-334. Overton, K., and Serif, G.S. (1981). Synthesis of L-fucose in thyroid tissue. Biochim. Biophys. Acta 675, 281-284. Palcic, M.M., Heerze, L.D., Srivastava, O.P., and Hindsgaul, O. (1989). A bisubstrate analog inhibitor for alpha(1-2)-fucosyltransferase. J. Biol. Chem. 264, 17174-17181. Pan, P.C., Chiu, P.C.N., Lee, C.L., Chang, L.Y., Panico, M., Moriss, H.R., Haslam, S.M., Khoo, K.H., Clark, G.F., Yeung, W.S.B., Dell, A. (2011). Human Sperm Binding Is Mediated by the Sialyl-Lewis x Oligosaccharide on the Zona Pellucida. Science 333, 1761-1764 Park, S.H., Pastuszak, I., Drake, R., and Elbein, A.D. (1998). Purification to apparent homogeneity and properties of pig kidney L-fucose kinase. J. Biol. Chem. 273, 5685-5691. Pastuszak, I., Ketchum, C., Hermanson, G., Sjoberg, E.J., Drake, R., and Elbein, A.D. (1998). GDP-L-fucose pyrophosphorylase. Purification, cDNA cloning, and properties of the enzyme. J. Biol. Chem. 273, 30165-30174. Prieels, J.P., Monnom, D., Dolmans, M., Beyer, T.A., and Hill, R.L. (1981). Co-purification of the Lewis blood group N-acetylglucosaminide alpha 1 goes to 4 fucosyltransferase and an N-acetylglucosaminide alpha 1 goes to 3 fucosyltransferase from human milk. J. Biol. Chem. 256, 10456-10463. Quirk, S., and Seley, K.L. (2005). Substrate discrimination by the human GTP fucose pyrophosphorylase. Biochemistry 44, 10854-10863. Rasko, D.A., Wang, G., Palcic, M.M., and Taylor, D.E. (2000). Cloning and characterization of the alpha(1,3/4) fucosyltransferase of Helicobacter pylori. J. Biol. Chem. 275, 4988-4994. Salmi, M., Granfors, K., MacDermott, R., and Jalkanen, S. (1994). Aberrant binding of lamina propria lymphocytes to vascular endothelium in inflammatory bowel diseases. Gastroenterology 106, 596-605. Sarnesto, A., Kohlin, T., Hindsgaul, O., Thurin, J., and Blaszczyk-Thurin, M. (1992). Purification of the secretor-type beta-galactoside alpha 1-2-fucosyltransferase from human serum. J. Biol. Chem. 267, 2737-2744. Sarnesto, A., Kohlin, T., Thurin, J., and Blaszczyk-Thurin, M. (1990). Purification of H gene-encoded beta-galactoside alpha 1-2 fucosyltransferase from human serum. J. Biol. Chem. 265, 15067-15075. Sasaki, K., Kurata, K., Funayama, K., Nagata, M., Watanabe, E., Ohta, S., Hanai, H., and Nishi, T. (1994). Expression cloning of a novel alpha 1,3-fucosyltransferase that is involved in biosynthesis of the sialyl Lewis x carbohydrate determinants in leukocytes. J. Biol. Chem. 269, 14730-14737. Sawa, M., Hsu, T.L., Itoh, T., Sugiyama, M., Hanson, S.R., Vogt, P.K., and Wong, C.H. (2006). Glycoproteomic probes for fluorescent imaging of fucosylated glycans in vivo. Proc. Natl. Acad. Sci. USA 103, 12371-12376. Schworer, R., and Schmidt, R.R. (2002). Efficient sialyltransferase inhibitors based on glycosides of N-acetylglucosamine. J. Am. Chem. Soc. 124, 1632-1637. Sell, S. (1990). Cancer-associated carbohydrates identified by monoclonal antibodies. Hum. Pathol. 21, 1003-1019. Shi, S., and Stanley, P. (2003). Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc. Natl. Acad. Sci. USA 100, 5234-5239. Somoza, J.R., Menon, S., Schmidt, H., Joseph-McCarthy, D., Dessen, A., Stahl, M.L., Somers, W.S., and Sullivan, F.X. (2000). Structural and kinetic analysis of Escherichia coli GDP-mannose 4,6 dehydratase provides insights into the enzyme's catalytic mechanism and regulation by GDP-fucose. Structure 8, 123-135. Staudacher, E. (1996). α1,3-Fucosyltransferases. Trends Glycosci. Glycotech. 8, 391-408. Stein, D.B., and Lin, Y.N. (2008). Characterization of Helicobacter pylori α1,2-Fucosyltransferase for Enzymatic Syntehsis of Tumor-Associated Antigens. Adv. Synth. Catal. 350, 2313-2321. Sullivan, F.X., Kumar, R., Kriz, R., Stahl, M., Xu, G.Y., Rouse, J., Chang, X.J., Boodhoo, A., Potvin, B., and Cumming, D.A. (1998). Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro. J. Biol. Chem. 273, 8193-8202. Sun, H.Y., Lin, S.W., Ko, T.P., Pan, J.F., Liu, C.L., Lin, C.N., Wang, A.H., and Lin, C.H. (2007). Structure and mechanism of Helicobacter pylori fucosyltransferase. A basis for lipopolysaccharide variation and inhibitor design. J. Biol. Chem. 282, 9973-9982. Taniguchi, N., Honke, K., and Fukuda, M. (2002). Handbook of Glycosyltransferases and Related Genes (Tokyo, Springer). Taylor-Papadimitriou, J., and Epenetos, A.A. (1994). Exploiting altered glycosylation patterns in cancer: progress and challenges in diagnosis and therapy. Trends Biotechnol. 12, 227-233. Tonetti, M., Sturla, L., Bisso, A., Benatti, U., and De Flora, A. (1996). Synthesis of GDP-L-fucose by the human FX protein. J. Biol. Chem. 271, 27274-27279. Wang, Q.Y., Wu, S.L., Chen, J.H., Liu, F., and Chen, H.L. (2003). Expressions of Lewis antigens in human non-small cell pulmonary cancer and primary liver cancer with different pathological conditions. J. Exp. Clin. Cancer Res. 22, 431-440. Wang, W., Hu, T., Frantom, P.A., Zheng, T., Gerwe, B., Del Amo, D.S., Garret, S., Seidel, R.D., and Wu, P. (2009). Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives. Proc. Natl. Acad. Sci. USA 106, 16096-16101. Wang, X., Gu, J., Ihara, H., Miyoshi, E., Honke, K., and Taniguchi, N. (2006). Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling. J. Biol. Chem. 281, 2572-2577. Wang, Y., Shao, L., Shi, S., Harris, R.J., Spellman, M.W., Stanley, P., and Haltiwanger, R.S. (2001). Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase. J. Biol. Chem. 276, 40338-40345. Weston, B.W., Smith, P.L., Kelly, R.J., and Lowe, J.B. (1992). Molecular cloning of a fourth member of a human a(1,3)fucosyltransferase gene family. J. Biol. Chem. 267, 24575–24584. Wittmann, V., and Wong, C.H. (1997). 1H-Tetrazole as Catalyst in Phosphomorpholidate Coupling Reactions: Efficient Synthesis of GDP-Fucose, GDP-Mannose, and UDP-Galactose. J. Org. Chem. 62, 2144-2147. Wolfenden, R. (1976). Transition state analog inhibitors and enzyme catalysis. Annu. Rev. Biophys. Bioeng. 5, 271-306. Wu, C.Y., Chang, C.F., Chen, J.S., Wong, C.H., and Lin, C.H. (2003). Rapid diversity-oriented synthesis in microtiter plates for in situ screening: discovery of potent and selective alpha-fucosidase inhibitors. Angew. Chem. Int. Ed. 42, 4661-4664. Wu, H.J., Ho, C.W., Ko, T.P., Popat, S.D., Lin, C.H., and Wang, A.H. (2010). Structural basis of alpha-fucosidase inhibition by iminocyclitols with K(i) values in the micro- to picomolar range. Angew. Chem. Int. Ed. 49, 337-340. Wyss, D.F., Choi, J.S., Li, J., Knoppers, M.H., Willis, K.J., Arulanandam, A.R., Smolyar, A., Reinherz, E.L., and Wagner, G. (1995). Conformation and function of the N-linked glycan in the adhesion domain of human CD2. Science 269, 1273-1278. Yanagidani, S., Uozumi, N., Ihara, Y., Miyoshi, E., Yamaguchi, N., and Taniguchi, N. (1997). Purification and cDNA cloning of GDP-L-Fuc:N-acetyl-beta-D-glucosaminide:alpha1-6 fucosyltransferase (alpha1-6 FucT) from human gastric cancer MKN45 cells. J. Biochem. 121, 626-632. Yi, W., Liu, X., Li, Y., Li, J., Xia, C., Zhou, G., Zhang, W., Zhao, W., Chen, X., Wang, P.G. (2009). Remodeling bacterial polysaccharides by metabolic pathway engineering. Proc. Natl. Acad. Sci. USA 106, 4207-4212. Zhao, G., Guan, W., Cai, L., and Wang, P.G. (2010). Enzymatic route to preparative-scale synthesis of UDP-GlcNAc/GalNAc, their analogues and GDP-fucose. Nat. Protoc. 5, 636-646. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16393 | - |
| dc.description.abstract | Fucosylated glycans are critical to a variety of cell events such as cell-cell adhesion, immune response, bacterial infection and tumor progression. Fucosyltransferases (FucTs) usually catalyze the final steps of glycosylation and are critical to many biological processes. High levels of specific FucT activities are often associated with various cancers. It is thus a promising approach to develop FucT inhibitors for potential anti-inflammatory and anti-tumor therapies is therefore a promising strategy.
Sugar nucleotide analogues are often potent glycosyltransferase inhibitors. Several GDP-L-Fucose (GDP-Fuc) analogues have been synthesized for the development of FucT inhibitors. However, it is notoriously difficult to synthesize and purify these molecules by conventional chemical synthesis. In this thesis, we developed one-step enzymatic synthesis of GDP-Fuc and analogues by utilizing a bifunctional enzyme fucokinase/GDP-fucose pyrophosphorylase (FKP) from Bacteroides fragilis. FKP contains a kinase domain and a pyrophosphorylase domain in a single peptide chain that catalyzes the phosphorylation of L-fucose to form L-fucose-1-phosphate and the subsequent conversion to GDP-Fuc. The process is simple as compared to the chemical method and is suitable for the synthesis at a preparative scale. FKP is a promiscuous enzyme for its broad substrate specificity toward the modifications at C-5 position of L-fucose. Successful synthesis of GDP-Fuc and its analogues including GDP-D-arabinose, GDP-L-galactose, GDP-N3-L-fucose and GDP-alkynyl-L-fucose was achieved with high yields (60-95%) and purities (>98% by HPLC). A multienyme synthesis involving CMP-sialic acid synthetase (NeuA), α-2,3-sialyltransferase (SiaT), α-1,3-FucT and FKP was carried out in one-pot and two-steps with in-situ cofactor regeneration for preparing of sLex. After simple steps of purification, sLex was obtained in a 90% yield. To discover promising FucT inhibitors, we developed a three-step chemoenzymatic method for rapid assembly of various GDP-Fuc derivatives from 6-azido-L-fucose. 6-Azido-L-fucose was converted to GDP-6-azido-L-fucose by FKP, followed by reduction to produce GDP-6-amino-L-fucose. The product was subjected to diversity-oriented synthesis, i.e., the amide-forming reactions with 94 carboxylic acids. The obtained GDP-Fuc derivatives were screened for inhibitory activity against H. pylori and human α-1,3-FucTs. Compounds incorporating appropriate hydrophobic moieties were identified from the initial screening, individually synthesized, purified and characterized for their inhibition kinetics. Compound 29 had a Ki of 29 nM for human FucT-VI, and is 269 and 11 times more selective than for H. pylori FucT (Ki = 7.8 μM) and for human FucT-V (Ki = 0.31 μM). | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T18:12:48Z (GMT). No. of bitstreams: 1 ntu-101-D94b46015-1.pdf: 13919381 bytes, checksum: 78554070a4044731091560ef9b4c364d (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Abstract I
Abbreviations IV Contents VI Chapter 1. Introduction 1.1 Fucosylation and Fucosyltransferase 2 1.2 Fucosylation and Disease 9 1.3 Catalytic Mechanism of Fucosyltransferase 11 1.4 Fucosyltransferase Inhibitor 12 1.5 Synthesis of GDP-Fuc and analogues 20 1.4 Specific Aims 25 Chapter 2. Enzymatic Synthesis of GDP-Fucose Analogues and Sialyl Lewis X 2.1 Experimental Section 2.1.1 Materials 29 2.1.2 Plasmid Construction, Protein Expression and Purification 29 2.1.3 Substrate Specificity of FKP 32 2.1.4 Kinetic Analysis of FKP 33 2.1.5 Enzymatic Synthesis of GDP-Fuc (20) and Analogues (21-24) 34 2.1.6 Purification of GDP-Fuc and Analogues 34 2.1.7 Enzymatic Synthesis of sLex (25) with In Situ Cofactor Regeneration 35 2.2 Results 2.2.1 Protein Expression and Purification 37 2.2.2 Enzyme Activity and Substrate Specificity of FKP 37 2.2.3 Enzymatic Synthesis of GDP-Fuc (20) and Analogues (21-24) 38 2.2.4 Enzymatic Synthesis of sLex (25) with In-Situ Cofactor Regeneration 41 2.3 Discussion 2.3.1 Enzyme Property of FKP 43 2.3.2 Enzymatic Synthesis of GDP-Fuc (20) and Analogues (21-24) 44 2.3.3 Comparison of FKP-catalyzed GDP-Fuc Synthesis with Other Approaches 45 2.3.4 Enzymatic Synthesis of sLex with In-Situ Cofactor Regeneration 48 2.4 Conclusions and Perspective 50 Chapter 3. Chemoenzymatic Synthesis of GDP-L-Fucose Derivatives as Potent and Selective α-1,3-Fucosyltransferase Inhibitors 3.1 Experimental Section 3.1.1 Material 52 3.1.2 Enzyme Preparation 53 3.1.3 Synthesis of GDP-6-amino-L-fucose (26) 54 3.1.4 Amide-Forming Reactions of GDP-Fuc Derivatives and FucT Activity Assay 55 3.1.5 Synthesis of Compounds 27–29 56 3.1.6 Measurement of IC50 and Ki Values 57 3.2 Results 3.2.1 Synthesis of GDP-6-amino-L-fucose (26) 58 3.2.2 Preparation of GDP-Fuc Derivatives and Screening for Inhibition activity 59 3.2.3 Evaluation of Inhibitory Activities of Compounds 27–29 61 3.3 Discussion 3.3.1 Synthesis of GDP-6-amino-L-fucose (26) 63 3.3.2 Preparation of GDP-Fuc Derivatives and Screening for Inhibition Activity 63 3.3.3 Evaluation of inhibitory activities of compounds 27–29 65 3.3.4 Molecular Modeling Study 67 3.3.5 GDP-Fuc Derivatives as FucT Inhibitors 73 3.4 Conclusions and Perspective 75 References 77 Appendix I. Structures of Carboxylic Acid and Ki Determination of the Inhibitor 89 Appendix II. NMR and Mass Spectra 99 Published Paper | |
| dc.language.iso | en | |
| dc.subject | 岩藻糖轉移酵素 | zh_TW |
| dc.subject | 酵素 | zh_TW |
| dc.subject | 酵素有機合成 | zh_TW |
| dc.subject | 抑制劑 | zh_TW |
| dc.subject | fucosyltransferase | en |
| dc.subject | chemoenzymatic synthesis | en |
| dc.subject | enzyme | en |
| dc.subject | inhibitor | en |
| dc.title | 酵素有機合成 GDP-L-Fucose 衍生物以作為岩藻糖轉移酵素抑制劑之開發 | zh_TW |
| dc.title | Chemoenzymatic Synthesis of GDP-L-Fucose Derivatives for the Development of α-1,3-Fucosyltransferase Inhibitors | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 方俊民(Jim-Min Fang),吳世雄(Shih-Hsiung Wu),楊進木(Jinn-Moon Yang),鄭婷仁(Ting-Jen Cheng) | |
| dc.subject.keyword | 酵素,酵素有機合成,抑制劑,岩藻糖轉移酵素, | zh_TW |
| dc.subject.keyword | enzyme,chemoenzymatic synthesis,inhibitor,fucosyltransferase, | en |
| dc.relation.page | 118 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2012-06-25 | |
| 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-101-1.pdf 未授權公開取用 | 13.59 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。