請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37085
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 方俊民(Jim-Min Fang) | |
dc.contributor.author | Peng-Hao Hsu | en |
dc.contributor.author | 徐鵬皓 | zh_TW |
dc.date.accessioned | 2021-06-13T15:18:57Z | - |
dc.date.available | 2014-08-17 | |
dc.date.copyright | 2011-08-17 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-11 | |
dc.identifier.citation | 1. Apweiler, R.; Hermjakob, H.; Sharon, N. Biochim. Biophys. Acta 1999, 1473, 4–8. On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database.
2. van Kooyk, Y.; Rabinovich, G. A. Nat. Immunol. 2008, 9, 593–601. Protein-glycan interactions in the control of innate and adaptive immune responses. 3. Stansell, E.; Desrosiers, R. C. Yale J. Biol. Med. 2010, 83, 201–208. Functional contributions of carbohydrate on AIDS virus glycoprotein. 4. Daniels, M. A.; Hogquist, K. A.; Jameson, S. C. Nat. Immunol. 2002, 3, 903–910. Sweet 'n' sour: the impact of differential glycosylation on T cell responses. 5. Janik, M. E.; Litynska, A.; Vereecken, P. Biochim. Biophys. Acta 2010, 1800, 545–555. Cell migration–The role of integrin glycosylation. 6. Varki, N. M.; Varki, A. Lab. Invest. 2007, 87, 851–857. Diversity in cell surface sialic acid presentations: implications for biology and disease. 7. Shinya, K.; Ebina, M.; Yamada, S.; Ono, M.; Kasai, N.; Kawaoka, Y. Nature 2006, 440, 435–436. Avian flu: influenza virus receptors in the human airway. 8. Angata, T.; Varki, A. Chem. Rev. 2002, 102, 439–470. Chemical diversity in the sialic acids and related α-keto acids: an evolutionary perspective. 9. Delmas, F.; Séveno, M.; Northey, J. G. B.; Hernould, M.; Lerouge, P.; McCourt, P.; Chevalier, C. J. Exp. Bot. 2008, 59, 2639–2647. The synthesis of the rhamnogalacturonan II component 3-deoxy-D-manno-2-octulosonic acid (Kdo) is required for pollen tube growth and elongation. 10. Troy, F. A. Glycobiology 1992, 2, 5–23. Polysialylation: from bacteria to brains. 11. Telang, S.; Vimr, E.; Mahoney, J. R.; Law, I.; Lundqvist-Gustafsson, H.; Qian, M.; Eaton, J. W. J. Infect. Dis. 2001, 184, 159–165. Strain-specific iron-dependent virulence in Escherichia coli. 12. Vogel, U.; Frosch, M. Mol. Microbiol. 1999, 32, 1133–1139. Mechanisms of neisserial serum resistance. 13. Rutishauser, U. Nat. Rev. Neurosci. 2008, 9, 26–35. Polysialic acid in the plasticity of the developing and adult vertebrate nervous system. 14. Erridge, C.; Bennett-Guerrero, E.; Poxton, I. R. Microb. Infect. 2002, 4, 837–851. Structure and function of lipopolysaccharides. 15. Raetz, C. R. H.; Whitfield, C. Annu. Rev. Biochem. 2002, 71, 635–700. Lipopolysaccharide endotoxins. 16. Osborn, M. J. Proc. Natl. Acad. Sci. USA 1963, 50, 499–506. Studies on the gram-negative cell wall, I. evidence for the role of 2-keto-3-deoxyoctonate in the lipopolysaccharide of Salmonella typhimurium. 17. Dröge, W.; Lehmann, V.; Lüderitz, O.; Westphal, O. Eur. J. Biochem. 1970, 14, 175–184. Structural investigations on the 2-keto-3-deoxyoctonate region of lipopolysaccharides. 18. Cooper, A. J. L.; Ginos, J. Z.; Meister, A. Chem. Rev. 1983, 83, 321–358. Synthesis and properties of the α-keto acids. 19. Inoue, S.; Lin, S.-L.; Lee, Y. C.; Inoue, Y. Glycobiology 2001, 11, 759–767. An ultrasensitive chemical method for polysialic acid analysis. 20. Mannerstedt, K.; Jansson, A. M.; Weadge, J.; Hindsgaul, O. Angew. Chem. Int. Ed. 2010, 49, 8173–8176. Small-molecule sensing: a direct enzyme-linked immunosorbent assay for the monosaccharide Kdo. 21. Huang, Y.-L.; Wu, C.-Y. Expert Rev. Vaccines 2010, 9, 1257–1274. Carbohydrate-based vaccines: challenges and opportunities. 22. Astronomo, R. D.; Burton, D. R. Nat. Rev. Drug Discov. 2010, 9, 308–324. Carbohydrate vaccines: developing sweet solutions to sticky situations? 23. Jennings, H. J.; Lugowski, C.; Ashton, F. E. Infect. Immun. 1984, 43, 407–412. Conjugation of meningococcal lipopolysaccharide R-type oligosaccharides to tetanus toxoid as route to a potential vaccine against group B Neisseria meningitidis. 24. Chu, C. Y.; Liu, B. K.; Watson, D.; Szu, S. S.; Bryla, D.; Shiloach, J.; Schneerson, R.; Robbins, J. B. Infect. Immun. 1991, 59, 4450–4458. Preparation, characterization, and immunogenicity of conjugates composed of the O-specific polysaccharide of Shigella dysenteriae type 1 (Shiga's bacillus) bound to tetanus toxoid. 25. Kubler-Kielb, J.; Vinogradov, E.; Ben-Menachem, G.; Pozsgay, V.; Robbins, J. B.; Schneerson, R. Vaccine 2008, 26, 3587–3593. Saccharide/protein conjugate vaccines for Bordetella species: Preparation of saccharide, development of new conjugation procedures, and physico-chemical and immunological characterization of the conjugates. 26. Robbins, J. B.; Kubler-Kielb, J.; Vinogradov, E.; Mocca, C.; Pozsgay, V.; Shiloach, J.; Schneerson, R. Proc. Natl. Acad. Sci. USA 2009, 106, 7974–7978. Synthesis, characterization, and immunogenicity in mice of Shigella sonnei O-specific oligosaccharide-core-protein conjugates. 27. Seid, R. C.; Sadoff, J. C. J. Biol. Chem. 1981, 256, 7305–7310. Preparation and characterization of detoxified lipopolysaccharide-protein conjugates. 28. Verheul, A. F.; Braat, A. K.; Leenhouts, J. M.; Hoogerhout, P.; Poolman, J. T.; Snippe, H.; Verhoef, J. Infect. Immun. 1991, 59, 843–851. Preparation, characterization, and immunogenicity of meningococcal immunotype L2 and L3,7,9 phosphoethanolamine group-containing oligosaccharide-protein conjugates. 29. Gu, X.-X.; Tsai, C.-M. Infect. Immun. 1993, 61, 1873–1880. Preparation, characterization, and immunogenicity of meningococcal lipooligosaccharide-derived oligosaccharide-protein conjugates. 30. Tao, C.-C. M.S. thesis, 2007, National Chung Hsing University. Searching for meningococcal antigens with vaccine potential. 31. Finne, J.; Leinonen, M.; Mäkelä, P. H. Lancet 1983, 322, 355–357. Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. 32. Granoff, D. M. Clin. Infect. Dis. 2010, 50, S54–S65. Review of meningococcal group B vaccines. 33. Wong, C.-H. Carbohydrate-based drug discovery; Wiley-VCH Verlag GmbH & Co. KGaA: 2005; pp 357–380. 34. Jennings, H.; Roy, R.; Gamian, A. J. Immunol. 1986, 137, 1708–1713. Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine. 35. Moe, G. R.; Bhandari, T. S.; Flitter, B. A. J. Immunol. 2009, 182, 6610–6617. Vaccines containing de-N-acetyl sialic acid elicit antibodies protective against Neisseria meningitidis groups B and C. 36. Pon, R. A.; Lussier, M.; Yang, Q.-L.; Jennings, H. J. J. Exp. Med. 1997, 185, 1929–1938. N-Propionylated group B meningococcal polysaccharide mimics a unique bactericidal capsular epitope in group B Neisseria meningitidis. 37. Jennings, H. J. Int. J. Infect. Dis. 1997, 1, 158–164. N-Propionylated group B meningococcal polysaccharide glycoconjugate vaccine against group B meningococcal meningitis. 38. Bruge, J.; Bouveret-Le Cam, N.; Danve, B.; Rougon, G.; Schulz, D. Vaccine 2004, 22, 1087–1096. Clinical evaluation of a group B meningococcal N-propionylated polysaccharide conjugate vaccine in adult, male volunteers. 39. Krug, L. M.; Ragupathi, G.; Ng, K. K.; Hood, C.; Jennings, H. J.; Guo, Z.; Kris, M. G.; Miller, V.; Pizzo, B.; Tyson, L.; Baez, V.; Livingston, P. O. Clin. Cancer Res. 2004, 10, 916–923. Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin. 40. Lai, P.-T. M.S. thesis, 2009, National Taiwan University. Iodine-promoted condensation of aldoses and α-ketoacid-terminated saccharides with o-phenylenediamines for synthesis of glycoconjugates. 41. Anumula, K. R. Anal. Biochem. 2006, 350, 1–23. Advances in fluorescence derivatization methods for high-performance liquid chromatographic analysis of glycoprotein carbohydrates. 42. Adamczyk, M.; Grote, J. Org. Prep. Proced. Int. 1995, 27, 239–242. A practical method for the synthesis of N-fluorenylmethoxycarbonyl diamine. 43. Atherton, E.; Bury, C.; Sheppard, R. C.; Williams, B. J. Tetrahedron Lett. 1979, 20, 3041–3042. Stability of fluorenylemthoxycarbonylamino groups in peptide synthesis. Cleavage by hydrogenolysis and by dipolar aprotic solvents. 44. Cheng, M.-C.; Lin, C.-H.; Lin, H.-J.; Yu, Y.-P.; Wu, S.-H. Glycobiology 2004, 14, 147–155. Hydrolysis, lactonization, and identification of α(2→8)/α(2→9) alternatively linked tri-, tetra-, and polysialic acids. 45. Hou, S.-J.; Saksena, R.; Kovác, P. Carbohydr. Res. 2008, 343, 196–210. Preparation of glycoconjugates by dialkyl squarate chemistry revisited. 46. Langenhan, J. M.; Thorson, J. S. Curr. Org. Synth. 2005, 59–81. Recent carbohydrate-based chemoselective ligation applications. 47. Cheng, M.-C. M.S. thesis, 2011, National Taiwan University. Synthesis, characterization, and immunogenicity of O-specific polysaccharide based glycan vaccine against Salmonella typhimurium. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37085 | - |
dc.description.abstract | 細菌表面之多醣與細菌感染中之致病機轉有關而常被選作醣疫苗之目標,但這些多醣需與蛋白質連結才能夠引發T 細胞媒介之免疫反應。在細菌表面之多醣中,多聚唾液酸和脂多醣是兩種具有還原端之酮酸醣的獨特多醣。儘管已經有許多方法可以應用在醣蛋白的合成,但針對酮酸醣之醣蛋白的合成方法則較為少見。
我們在這裡描述一個方法,藉由丙酮酸和鄰苯二胺的縮合反應及硫醇對馬來醯亞胺(maleimide)的Michael 加成反應來連結酮酸醣與蛋白質。我們的結果指出酮酸醣單醣、雙醣和多醣都可與帶有末端胺基的鄰苯二胺連接劑有效率地進行縮合反應,而產生之喹喔啉酮(quinoxalinone)衍生物可再修飾上末端的硫醇,最後的Michael 加成反應即可將帶有末端硫醇之唾液酸喹喔啉酮衍生物與修飾有馬來醯亞胺的牛血清蛋白進行連結。在多聚唾液酸的例子中,我們可成功得到其帶有末端硫醇之喹喔啉酮衍生物,但多聚唾液酸與牛血清蛋白的連結卻失敗。未來多聚唾液酸與牛血清蛋白之連結物的製備仍會繼續嘗試,而這樣的多聚唾液酸醣蛋白有希望可以應用於對抗B 型腦膜炎雙球菌之疫苗。 | zh_TW |
dc.description.abstract | Bacterial surface polysaccharides are virulent agents for bacterial infection and often chosen as the target of carbohydrate-based vaccines; however, these polysaccharides need to be conjugated to proteins to elicit T-cell mediated immune response. Among bacterial surface polysaccharides, polysialic acid (PSA) and lipopolysaccharide (LPS) are unique in that their terminal saccharides are α-ketoacids. Although there are many methods for conjugation of glycoproteins, the corresponding conjugation methods for α-ketoacid-based glycoproteins are less common.
We report here a method for conjugation of α-ketoacid saccharides with proteins by using condensation reactions of α-ketoacid with o-phenylenediamine (OPD) and Michael addition of thiol to maleimide (MA). Our results showed that α-ketoacid mono-, di-, and polysaccharides were efficiently condensed with the OPD linker bearing a terminal amino group. These saccharide quinoxalinone derivatives were then modified with a terminal thiol, and the subsequent Michael addition furnished the conjugation of thiol-terminated sialic acid–quinoxalinone derivative to MA-modified bovine serum albumin (MA–BSA). In the case of NPrPSA, a α-ketoacid polysaccharide, its quinoxalinone derivative bearing terminal thiol was prepared, but the subsequent conjugation to MA–BSA failed with unclear reason. The preparation of NPrPSA–BSA conjugate as a vaccine against group B Neisseria meningitidis may be attempted in a different approach. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:18:57Z (GMT). No. of bitstreams: 1 ntu-100-R98223152-1.pdf: 9477131 bytes, checksum: 49b33fb7a047e3ed2e650d05fafc6d79 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | Acknowledgement I
Abstract in Chinese III Abstract in English IV Table of contents VI Index of Schemes IX Index of Figures XI Index of Tables XII Abbreviations XIII Chapter 1. Introduction 1 1.1 Carbohydrates 1 1.2 α-Ketoacid saccharides 1 1.3 α-Ketoacid-terminated polysaccharides 3 1.3.1 Polysialic acid 3 1.3.2 Lipopolysaccharide 5 1.4 Condensation of o-phenylenediamines with α-ketoacids 7 1.5 Carbohydrate-based vaccines 9 1.6 Methods for synthesis of α-ketoacid saccharide-based glycoproteins 10 1.6.1 Reductive amination 11 1.6.2 Oxime linkage 13 1.6.3 Amide bond formation 15 1.6.4 Summary of synthetic methods of α-ketoacid saccharide-based glycoproteins 17 1.7 Vaccines against group B Neisseria meningitidis 19 Chapter 2. Results and Discussion 27 2.1 Previous research 27 2.2 Optimization of condensation reaction of α-ketoacid saccharides with o-phenylenediamine 27 2.3 Design and synthesis of o-phenylenediamine linkers 30 2.4 Condensation of α-ketoacid saccharide with o-phenylenediamine linker 33 2.5 Synthesis of quinoxalinones derivatives bearing terminal thiol 35 2.6 Conjugation of quinoxalinones derived from α-ketoacid saccharides to proteins 41 2.7 Synthesis of NPrPSA–BSA conjugates 44 2.8 Conclusion 53 2.9 Future application 54 Chapter 3. Experimental Section 56 3.1 General part 56 3.2 General procedure for condensation reaction of α-ketoacid saccharides with o-phenylenediamine or its derivatives 57 3.3 Bio-Rad protein test 58 3.4 Ellman’s assay 58 3.5 SDS-PAGE electrophoresis 58 3.6 Synthesis and Characterization of Compounds 60 References 80 Appendix 88 | |
dc.language.iso | en | |
dc.title | 使用鄰苯二胺連接劑連結酮酸醣與蛋白質之方法以研究製備對抗B型腦膜炎雙球菌之疫苗 | zh_TW |
dc.title | Conjugation of α-Ketoacid Saccharides with Proteins Using o-Phenylenediamine Linkers: An Approach to Vaccines against Group B Neisseria meningitidis | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳宗益,楊文彬,羅禮強 | |
dc.subject.keyword | 酮酸醣,鄰苯二胺,喹,喔啉,酮,醣蛋白,疫苗,B型腦膜炎雙球菌, | zh_TW |
dc.subject.keyword | α-ketoacid saccharide,o-phenylenediamine,quinoxalinone,glycoprotein,vaccine,group B Neisseria meningitidis, | en |
dc.relation.page | 101 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-11 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 化學研究所 | zh_TW |
顯示於系所單位: | 化學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-100-1.pdf 目前未授權公開取用 | 9.26 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。