結合化學與酵素方法合成多醣體｜國立清華大學博碩士論文庫

簡易檢索 / 詳目顯示

回結果列表

研究生：	蕭偉鎮 Hsiao, Wei-Chen
論文名稱：	結合化學與酵素方法合成多醣體 Chemoenzymatic Synthesis of Oligosaccharides
指導教授：	林俊成 Lin, Chun-Cheng
口試委員:	李耀坤蒙國光陳建添王聖凱林俊成
學位類別：	博士 Doctor
系所名稱：	理學院 - 化學系 Department of Chemistry
論文出版年：	2014
畢業學年度：	103
語文別：	中文
論文頁數：	154
中文關鍵詞：	醣類抗原、化學-酵素合成
外文關鍵詞：	Siglecs, chemoenzymatic synthesis
相關次數：	點閱：2 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

本研究利用有機合成及酵素催化之合成策略，結合前者之高變化性與後者之高專一性，成功提升合成效率。第一部分為合成腫瘤相關醣體抗原SSEA-5以及DSGb5，利用酵素(GalK、RmlA及LgtC)建構高挑戰性的Gal-1,4-Lac鍵結以合成Gb3三醣體。Gb3進一步與雙醣進行[2+3]醣基化反應，移除保護基後得到乳癌相關抗原SSEA-3。將五醣中間體以有機合成方式於N-乙醯半乳糖胺六號位置連接唾液酸，再利用唾液酸轉移酶於半乳糖三號位置建構另一唾液酸後，便得到腎臟癌抗原DSGb5，本論文為首次完成DSGb5之全合成。
第二部分為建構唾液酸化多醣體分子庫，以測試醣體唾液酸化之不同位置、數量，期望能提供一分子庫對Siglecs (Sialic acid-binding Ig-like lectins)的結合性。探討於Gal-1,3-GalNAc骨架上三個可供唾液酸化之位置，分別為GalNAc六號、Gal三號及Gal六號位置，依其排列組合共合成七種不同的醣體。透過有機合成與酵素催化之方法完成系列唾液酸化多醣體之合成，後續將以微陣列晶片檢驗醣體結構與Siglecs之結合力。

Chemoenzymatic synthesis, which combines the structural flexibility of organic synthesis and high specificity and efficacy of enzymatic synthesis, is applied in this research to synthesize oligosaccharides effectively. Herein, tumor-associated carbohydrate antigens SSEA-3, DSGb5, and multisialylated oligosaccharides library were synthesized by chemoenzymatic strategy. The syntheses of tumor-associated antigens were performed by first using enzymes GalK, and RmlA to generate UDP-Gal and LgtC to catalyze the formation of Gal-1,4-Lac linkage to give trisaccharide-Gb3. Following by chemical glycosylation of protected Gb3 with disaccharide and stepwise deprotection, SSEA-3 was acquired in 10 steps from Gb3 with total yield 23%. Then, SSEA-3 underwent chemical sialylation giving monosialylayed hexasaccharide and then enzymatic transformation by gave 2,3- sialyltransferase renal carcinoma antigen DSGb5 to accomplish the first total synthesis of DSGb5.
In the construction of multisialylated oligosaccharide library, the core structure, Gal-1,3-GalNAc, was sialylated by chemoenzymatic strategy. The library was composed of seven oligosaccharides differed by the number (or position) of sialylated sites. These oligosaccharides will be immobilized on microarray slide and their binding affinities with Siglecs are undergoing.

摘要 ........................................................................................................... I
Abstract..................................................................................................... II
縮寫表&中英對照表 ............................................................................... III
表目錄 ...................................................................................................... X
第一章、腫瘤相關醣體抗原SSEA-3 之合成 ......................................... 1
1-1 癌症相關醣體抗原 .............................................................. 1
1-2 Globo 系列抗原疫苗開發潛力探討 ................................... 5
1-3 Globo H 相關合成分析 ....................................................... 7
1-4 酵素合成建構Gal1,4-Lac 醣苷鍵 ................................. 19
1-5 順式二醇(cis-diol)活化試劑 ............................................. 23
1-6 研究目的與構想 ............................................................... 25
1-7 逆合成分析 ....................................................................... 25
1-8 結果與討論 ........................................................................ 26
1-8-1 合成半乳糖衍生物 .................................................. 26
1-8-2 酵素合成Gb3 衍生物 ............................................. 28
1-8-3 醣受體33 合成 ........................................................ 31
1-8-4 醣予體32 合成 ........................................................ 34
1-8-5 [2+3]醣基化反應 ..................................................... 36
1-9 結論 .................................................................................... 43
第二章、腫瘤相關醣體抗原DSGb5 之合成 ......................................... 44
2-1 腎臟癌相關醣類抗原 ........................................................ 44
2-2 唾液酸 ................................................................................ 45
2-3 唾液酸化學合成方法分析 ................................................ 46
2-3-1 離去基效應 .............................................................. 47
2-3-2 溶劑效應 .................................................................. 50
2-3-3 唾液酸五號位置保護基 .......................................... 52
2-4 唾液酸酵素合成分析 ........................................................ 55
2-4-1 胞苷單磷酸唾液酸合成酶(CMP-Sialic Acid
Synthetase) ............................................................... 56
2-4-2 巴德氏桿菌-2,3-唾液酸轉移酶(Pm2,3ST) .......... 57
2-4-3 發光桿菌-2,6-唾液酸轉移酶(Pd2,6ST) ............... 59
2-5 研究目的與構想 ............................................................... 61
2-6 逆合成分析 ....................................................................... 61
VI
2-7 結果與討論 ........................................................................ 62
2-7-1 唾液酸予體之合成 .................................................. 63
2-7-2[5+1]唾液酸化反應 .................................................. 65
2-8 結論 ................................................................................... 70
第三章、唾液酸化醣體分子庫之建構 .................................................. 71
3-1 唾液酸結合性免疫球蛋白樣凝集素 ................................ 71
3-1-1 唾液酸結合性免疫球蛋白樣凝集素-4 ................... 74
3-1-2 唾液酸結合性免疫球蛋白樣凝集素-7 ................... 75
3-1-3 唾液酸結合性免疫球蛋白樣凝集素-14 ................. 76
3-1-4 唾液酸結合性免疫球蛋白樣凝集素-15 ................. 77
3-2 非天然唾液酸化醣體分子庫 ............................................ 78
3-3 研究目的與構想 ............................................................... 83
3-4 結果與討論 ........................................................................ 84
3-4-1 合成路徑分析 .......................................................... 84
3-4-2 化合物68 之合成 ................................................... 85
3-4-3 化合物69 之合成 ................................................... 87
3-4-4 化合物68 衍生之醣體合成 ................................... 87
3-4-5 化合物69 衍生之醣體合成 ................................... 88
3-4-6 核磁共振光譜鑑定各醣體之討論 .......................... 90
3-4-7 醣體結構對於唾液酸轉移酶之反應性比較 .......... 97
3-4-8 改變醣體還原端末端胺基之策略 .......................... 99
3-5 結論 .................................................................................. 100
第四章、未來展望 ................................................................................ 101
第五章、實驗部分 ................................................................................ 102
4-1 Meterial and methods ....................................................... 102
4-2 Synthetic procedures and characterization....................... 104
第六章、參考文獻 ................................................................................ 146
VII
圖目錄
圖一、mucin type 腫瘤相關抗原 ........................................................... 2
圖二、醣苷神經胺基脂類(glycosphingolipid) ....................................... 2
圖三、Ganglio-系列醣體結構示意圖..................................................... 3
圖四、Globo 系列醣體結構示意圖 ........................................................ 3
圖五、Lacto-系列醣體結構示意圖 ........................................................ 4
圖六、SSEA-3、SSEA-4 與Globo H 結構圖 ........................................ 6
圖四、Globo 系列醣體結構示意圖 ........................................................ 8
圖七、反應性梯度一鍋化合成策略。 ................................................. 13
圖八、酵素合成UDP-Gal 路徑圖 ........................................................ 20
圖九、GalK 受質轉換效率比較 ........................................................... 21
圖十、RmlA 對各受質長時間與短時間轉換效率比較 ...................... 22
圖十一、P1 antigen 結構圖 .................................................................. 22
圖十二、硼酸衍生物催化順式二醇選擇性進行多種反應 ................. 24
圖十三、化合物38 氫核磁共振光譜 ................................................... 30
圖十四、化合物38 之COSY 光譜 ...................................................... 31
圖十五、(a)4,6-及(b)3,4-丙酮縮醛氫核磁共振光譜之比較 ............... 32
圖十六、化合物50 COSY 二維光譜圖 ............................................... 35
圖十七、化合物50 COSY 光譜圖 ....................................................... 36
VIII
圖十八、化合物51 之HPLC 分析圖................................................... 37
圖十九、化合物52 之HPLC 分析圖................................................... 38
圖二十、化合物52 於不同氘溶劑中氫核磁共振光譜之比較 ........... 39
圖二十一、化合物32、33 與52 碳核磁共振光譜之比較 ................. 40
圖二十二、化合物52 HMQC 光譜圖 .................................................. 41
圖二十三、化合物53 HMQC 光譜圖 .................................................. 41
圖二十四、Troc 去保護反應機構 ........................................................ 42
圖二十五、腎臟癌相關醣體抗原結構圖 ............................................. 44
圖二十六、自然界主要三種唾液酸 ..................................................... 46
圖二十七、溶劑效應 ............................................................................ 51
圖二十八、化合物66 氫耦合碳譜 ....................................................... 67
圖二十九、碳核磁共振光譜分析Troc 與乙醯基之轉換 .................... 68
圖三十、Siglec 結構示意圖 .................................................................. 72
圖三十一、MAG 抑制軸突細胞再生機制圖 ....................................... 75
圖三十二、成對受器Siglec-5 與Siglec-14 ......................................... 77
圖三十三、Siglec-15 與sTn 結合後誘發表現TGF-之示意圖 ......... 78
圖三十四、O-linked 及N-linked 相關唾液酸化醣體衍生物 .............. 80
圖三十五、化合物73 氫耦合碳核磁共振光譜 ................................... 86
圖三十六、醣體六號位置唾液酸化氫核磁共振光譜(一) ................... 90
IX
圖三十七、醣體六號位置唾液酸化氫核磁共振光譜(二) ................... 91
圖三十八、醣體六號位置唾液酸化碳核磁共振光譜(一) ................... 93
圖三十九、醣體六號位置唾液酸化碳核磁共振光譜(二) ................... 94
圖四十、多醣體變旋異構碳比較圖 ..................................................... 96
圖四十一、多重唾液酸化醣體分子庫 ............................................... 100
                                

. Springer, G. F. Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J. Mol. Med. 1997, 75, 594-602.
. Hakomori, S.; Zhang, Y. Glycosphingolipid antigens and cancer therapy. Chem. Biol. 1997, 3, 97-104.
. Dube, D. H.; Bertozzi, C. R. Glycans in cancer and inflammation potential for Therapeutics and Diagnostics. Nat. Rev. Drug Discov. 2005, 4, 477-488.
. Slovin, S. F.; Ragupathi, G.; Adluri, S.; Ungers, G.; Terry, K.; Kim, S.; Spassova, M.; Bornmann, W. G.; Fazzari, M.; Dantis, L.; Olkiewicz, K.; Lloyd, K. O.; Livingston, P. O.; Danishefsky, S. J.; Scher, H. I. Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. Proc. Natl. Acad. Sci. USA 1999, 96, 5710-5715.
. Gilewski, T.; Ragupathi, G.; Bhuta, S.; Williams, L. J.; Musselli, C.; Zhang, X. F.; Bencsath, K. P.; Panageas, K. S.; Chin, J.; Hudis, C. A.; Norton, L.; Houghton, A. N.; Livingston, P. O.; Danishefsky, S. J. Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial. Proc. Natl. Acad. Sci. USA 2001, 98, 3270-3275.
. Wilson, R. M.; Danishefsky, S. J. A vision for vaccines built from fully synthetic tumor-associated antigens: From the laboratory to the clinic. J. Am. Chem. Soc. 2013, 135, 14462-14472.
. Bremer, E. G.; Levery, S. B.; Sonnino, S.; Ghidoni, R.; Canevari, S.; Kannagi, R.; Hakomori, S. Characterization of a glycosphingolipid antigen defined by the monoclonal antibody MBrl expressed in normal and neoplastic epithelial cells of human mammary gland. J. Biol. Chem. 1984, 259, 14773-14777.
. Zhang, S.; Zhang, H.; Reuter, V.; Solvin, S.; Scher, H.; Livngston, P. O. Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancer. Clin. Cancer Res. 1998, 4, 295-302.
. Zhang, S.; Cordon-Cardo, C.; Zhang, H. S.; Reuter, V. E.; Adluri, S.; Hamilton, W. B.; Lloyd, K. O.; Livingston, P. O.; Selection of tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides. Int. J. Cancer 1997, 73, 42-49.
. Kannagi, R.; Cochran, N. A.; Ishigami, F.; Hakomori, S.; Andrews, P. W.; Knowles, B. B.; Solter, D. Stage-specific embryonic antigens (SSEA-3 and -4) are epitopes of a unique globo-series ganglioside isolated from human teratocarcinoma cells. The EMBO Journal 1983, 2, 2355-2361.
. Ohyama, C.; Orikasa, S.; Kawamura, S.; Satoh, H.; Saito, S.; Fukushi, Y.; Levery, S. B.; Hakomori, S. Galactosylgloboside expression in seminoma. Inverse correlation with metastatic potential. Cancer 1995, 76, 1043-1050.
. Suzuki, Y.; Haraguchi, N.; Takahashi, H.; Uemura, M.; Nishimura, J.; Hata, T.; Takemasa, I.; Mizushima, T,; Ishii, H.; Doki, Y.; Mori, M.; Yamamoto, H. SSEA-3 as a novel amplifying cancer cell surface marker in colorectal cancers. Int. J. Oncol. 2013, 42, 161-167.
. Lou, Y. W.; Wang, P. Y.; Yeh, S. C.; Chuang, P. K.; Li, S. T.; Wu, C. Y.; Khoo, K. H.; Hsiao, M.; Hsu, T. L.; Wong, C. H. Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers. Proc. Natl. Acad. Sci. USA 2014, 111, 2482-2487.
. 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 transferase 1 and 2 in Globo H synthesis. Proc. Natl. Acad. Sci. USA 2008, 105, 11667-11672.
. Huang, Y. L.; Hung, J. T.; Cheung, K. C.; Lee, H. Y.; Chu, K. C.; Li, S. T.; Lin, Y. C.; Ren, C. T.; Cheng, T. J.; 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. USA 2013, 110, 2517-2522.
. Bilodeau, M. T.; Park, T. K.; Hu, S.; Randolph, J. T.; Danishefsky, S. J.; Livingston, P. O.; Zhang, S. Total synthesis of a human breast tumor associated antigen. J. Am. Chem. Soc. 1995, 117, 7840-7841.
. Allen, J. R.; Allen, J. G.; Zhang, X. F.; Williams, L. J.; Zatorski, A.; Ragupathi, G.; Livingston, P. O.; Danishefsky, S. J. A second generation synthesis of the MBr1 (Globo H) breast tumor antigen: New application of the n-pentenyl glycoside method for achieving complex carbohydrate protein linkages. Chem. Eur. J. 2000, 6, 1366-1375.
. Jeon, I.; Iyer, K.; Danishefsky, S. J. A practical total synthesis of Globo-H for use in anticancer vaccines. J. Org. Chem. 2009, 74, 8452-8455.
. Lassaletta, J. M.; Schmidt, R. R.; Synthesis of complex glycosphingolipid of the globo series. Liebigs Ann. Chem. 1996, 1417-1423.
. Zhu, T.; Boons, G. J. A two-directional and highly convergent approach for the synthesis of the tumor-associated antigen Globo-H. Angew. Chem. Int. Ed. 1999, 38, 3495-3497.
. Douglas, N. L.; Ley, S. V.; Lucking, U.; Warriner, S. L. Tuning glycoside reactivity: New tool for efficient oligosaccharide synthesis. J. Chem. Soc., Perkin Trans. 1 1998, 51-66
. Zhang, Z.; Ollmann, I. R.; Ye, X. S.; Wischnat, R.; Baasov, T.; Wong, C. H. Programmable one-pot oligosaccharide synthesis. J. Am. Chem. Soc. 1999, 121,734-753.
. Burkhart, F.; Zhang, Z.; Wacowich-Sgarbi, S.; Wong, C. H.; Synthesis of the Globo H hexasaccharide using the programmable reactivity-based one-pot strategy. Angew. Chem. Int. Ed. 2001, 40, 1274-1277.
. Huang, C. Y.; Thayer, D. A.; Chang, A. Y.; Best, M. D.; Hoffmann, J.; Head, S.; Wong, C. H. Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen. Proc. Natl. Acad. Sci. USA 2006, 103, 15-20.
. Wang, Z.; Zhou, L.; El-Boubbou, K.; Ye, X. S.; 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.
. Bosse, F.; Marcaurelle, L. A.; Seeberger, P. H. Linear synthesis of the tumor-associated carbohydrate antigens Globo H, SSEA-3, and Gb3. J. Org. Chem. 2002, 67, 6659-6670.
. Werz, D. B.; Castagner, B.; Seeberger, P. H. Automated synthesis of the tumor-associated carbohydrate antigens Gb-3 and Globo-H: Incorporation of -galactosidic linkages. J. Am. Chem. Soc. 2007, 129, 2770-2771.
. 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.
. 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.
. 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.
. 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.
. Chien, W. T.; Liang, C. F.; Yu, C. C.; Lin, J. H.; Wu, H. T.; Lin, C. C. Glucose 1-phosphate thymidylyltransferase in the synthesis of uridine 5’-diphosphate galactose and its application in the synthesis of N-acetyllactosamine. Adv. Synth. Catal. 2012, 354, 123-132.
. Timmons, S. C.; Mosher, R. H.; Knowles, S. A.; Jakeman, D. L. Exploiting nucleotidylyl transferases to prepare sugar nucleotides. Org. Lett. 2007, 9, 857-860.
. Zhang, J. B.; Kowal, P.; Fang, J. W.; Andreana, P.; Wang, P. G. Efficient chemoenzymatic synthesis of globotriose and its derivatives with a recombinant alpha-(1->4)-galactosyltransferase. Carbohydr. Res. 2002, 337, 969-976.
. Xu, H.; Lu, Y.; Zhou, Y.; Ren, B.; Pei, Y.; Dong, H.; Pei, Z. Regioselective benzylation of diols and polyols by catalytic amounts of an organotin reagent. Adv. Synth. Catal. 2014, 356, 1735-1740.
. Dong, H.; Zhou, Y.; Pan, X.; Cui, F.; Liu, W.; Liu, J.; Ramstrom, O. Stereoelectronic control in regioselective carbohydrate protection. J. Org. Chem. 2012, 77, 1457-1467.
. Muramatsu, W. Chemo- and regioselective monosulfonylation of nonprotected carbhydrates catalyzed by organotin dichloride under mild conditions. J. Org. Chem. 2012, 77, 8083-8091.
. Muramatsu, W.; Yoshimatsu, H. Regio- and stereochemical controlled Koenigs–Knorr-type monoglycosylation of secondary hydroxy groups in carbohydrates utilizing the high site recognition ability of organotin catalysts. Adv. Synth. Catal. 2013, 355, 2518-2524.
. Gouliaras, C.; Lee, D.; Chan, L.; Taylor, M. S., Regioselective activation of glycosyl acceptors by a diarylborinic acid-derived catalyst. J. Am. Chem. Soc. 2011, 133, 13926-13929.
. Lee, D.; Taylor, M. S. Borinic Acid-Catalyzed Regioselective acylation of carbohydrate derivatives. J. Am. Chem. Soc. 2011, 133, 3724-3727.
. Chan, L.; Taylor, M. S. Regioselective alkylation of carbohydrate derivatives catalyzed by a diarylborinic acid derivative. Org. Lett. 2011, 13, 3090-3093.
. Lee, D.; Williamson, C. L.; Chan, L.; Taylor, M. S. Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: Expansion of substrate scope and mechanistic studies. J. Am. Chem. Soc. 2012, 134, 8260-8267.
. 官亭君，國立清華大學化學研究所，博士論文，合成硫鍵結之-2,8唾液酸寡醣體與GD3抗原，民國103年。
. Lin, C. C.; Jan, M. D.; Weng, S. S.; Lin, C. C.; Chen, C. T. O-Isopropylidenation of carbohydrates catalyzed by vanadyl triflate. Carbohydr. Res. 2006, 341, 1948-1953.
. Busse, H.; Hakoda, M.; Stanley, M.; Streicher, H. Galactose- phosphonates as mimetics of the sialyltranfer by trypanosomal sialidase. J. Carbohyd. Chem. 2007, 26, 159-194.
. Sun, B.; Jiang, H. An efficient approach for total synthesis of aminopropyl functionalized ganglioside GM1b. Tetrahedr. Lett. 2012, 53, 5711-5715.
. Huang, L. D.; Lin, H. J. ; Huang, P. H.; Hsiao, W. C.; Raghava Reddy, L. V. ; Fu, S. L. ; Lin, C. C. Synthesis of serine-based glycolipids as potential TLR4 activators. Org. Biomol. Chem. 2011, 9, 2492–2504.
. Kocienski, P. J. Protecting groups, 3rd Ed.; Thieme: Stuttgart, New York, 2005; pp 8-9.
. Ito, A.; Handa, K.; Withers, D. A.; Satoh, M.; Hakomori, S. I. Binding specificity of siglec-7 to disialogangliosides of renal cell carcinoma: possible rule of disialogangliosides in tumor progressing. FEBS Letters 2001, 489, 116-120.
. Miyazaki, K.; Ohmori, K.; Izawa, M.; Koike, T.; Kumamoto, K.; Furukawa, K.; Ando, T.; Kiso, M.; Yamaji, T.; Hashimoto, Y.; Suzuki, A.; Yoshida, A.; Takeuchi, M.; Kannagi, R. Loss of disialyl Lewisa, the ligand for lymphocyte inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) associated with increased sialyl Lewisa expression on human colon cancers. Cancer Res. 2004, 64, 4498-4505.
. Saito, S.; Egawa, S.; Endoh, M; Ueno, S.; Ito, A.; Numahata, K.; Satoh, M.; Kuwao, S.; Baba, S.; Hakomori, S.; Arai, Y. RM2 antigen (1,4-GalNAc-disialyl-Lc4) as a new marker for prostate cancer. Int. J. Cancer 2005, 115, 105-113.
. Wu, C. S.; Yen, C. J.; Chou, R. H.; Li, S. T.; Huang, W. C.; Ren, C. T.; Wu, C. Y.; Yu, Y. L. Cancer-associated carbohydrate antigens as potential biomarkers for hepatocellular carcinoma. PLoS ONE, 7, e39466.
. 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.
. Crockers, P. R.; Varki, A. Immunology 2001, 103, 137-145.
. Varki, A. Glycobiology 1993, 3, 97-130.
. De Meo, C.; Demchenko, A. V.; Boons, G. J. A stereoselective approach for the synthesis of a-sialosides. J. Org. Chem. 2001, 66, 5490-5497.
. Premathilake, H. D.; Gobble, C. P.; Pornsuriyasak, P.; Hardimon, T.; Demchenko, A. V.; De Meo, C. How O-substitution of sialyl donors affects their stereoselectivity. Org. Lett. 2012, 14, 1126-1129.
. Kondo, H.; Ichikawa, Y.; Wong, C. H. -Sialyl phosphite and phosphoramidite: Synthesis and application to the chemoenzymatic synthesis of CMP-sialic acid and sialyl oligosaccharides. J. Am. Soc. Chem. 1992, 114, 8748-8750.
. Lin, C. C.; Huang, K. T.; Lin, C. C. N-trifluoroacetyl sialyl phosphite donors for the Synthesis of (2->9) oligosialic acid. Org. Lett. 2005, 7, 4169-4172.
. Hsu, C. H.; Chu, K. C.; Lin, Y. S.; Han, J. L. Peng, Y. S.; Ren, C. T.; Wu, C. Y.; Wong, C. H. Highly alpha-selective sialyl phosphate donors for efficient preparation of natural sialoside. Chem. Eur. J. 2010, 16, 1754-1760.
. Cai, S.; Yu, B. Efficient sialylation with phenyltrifluoroacetimidates as leaving groups. Org. Lett. 2003, 5, 3827-3830.
. Crich, D.; Li, W. -Selective sialylation at -78oC in nitrile solvents with a 1-adamantanyl thiosialoside. J. Org. Chem. 2007, 72, 7794-7797.
. Yu, C. S.; Niikura, K.; Lin, C. C.; Wong, C. H. The thioglycoside and glycosyl phosphite of 5-azido sialic acid: Excellent donors for the -glycosylation of primary hydroxy groups. Angew. Chem. Int. Ed. 2001, 40, 2900-2903.
. Tanaka, H.; Adachi, M.; Takahashi, T. One-pot synthesis of sialo-containing glycosyl amino acid by use of an N-trichloroethoxycarbonyl--thiophenyl sialoside. Chem. Eur. J. 2005, 11, 849-862.
. Tanaka, H.; Nishiura, Y.; Takahashi, T. Stereoselective synthesis of oligo--(2,8)-sialic acids. J. Am. Soc. Chem. 2006, 128, 7124-7125.
. Knorst, M.; Fessner, W. D. CMP-Sialate synthetase from Neisseria meningitides-overexpression and application to the synthesis of oligosaccharides containing modified sialic acids. Adv. Synth. Catal. 2001, 343, 698-710.
. Morley, T. J.; Withers, S. G. Chemoenzymatic synthesis and enzymatic analysis of 8-modified cytidine monophosphate-sialic acid and sialyl lactose derivatives. J. Am. Soc. Chem. 2010, 132, 9430-9437.
. 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. Soc. Chem. 2005, 127, 17618-17619.
. Yu, H.; Huang, S.; Chokhawala, H.; Sun, M.; Zheng, H.; Chen, X. Highly efficient chemoenzymatic synthesis of naturally occurring and non-natural -2,6- linked sialosides: A P. damsela -2,6- Sialyltransferase with extremely flexible donor–substrate specificity. Angew. Chem. Int. Ed. 2006, 45, 3938-3944.
. Huang, C. Y.; Wang, N.; Fujiki, K.; Otsuka, Y,; Akamatsu, M.; Fujimoto, Y.; Fukase, K. Wildly applicable deprotection method of 2,2,2-trichloroethoxycarbonyl (Troc) group using tetrabutylam- monium fluoride. J. Carbohydr. Chem. 2010, 29, 289-298.
. Hori, H.; Nakajima, T.; Nishida, Y.; Ohrui, H.; Meguro, H. A simple method to determined the anomeric configuration of sialic acid and its derivatives by 13C-NMR. Tetrahedron Lett. 1988, 29, 6317-6320.
. Pillai, S.; Netravali, I. A.; Cariappa, A.; Mattoo, H. Siglecs and immune regulation. Annu. Rev. Immunol. 2012, 30, 357-392.
. Crocker, P. R.; Paulson, J. C.; Varki, A. Siglecs and their roles in the immune system. Nat. Rev. Immunol.2007, 7, 255-266.
. 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.
. Otipoby, K. L.; Andersson, K. B.; Draves, K. E.; Klaus, S. J.; Farr, A. G.; Kerner, J. D.; Perlmutter, R. M.; Law, C. L.; Clark, E. A. CD22 regulates thymus-independent responses and the lifespan of B cells. Nature 1996, 384, 634-637.
. Biedermann, B.; Gil, D.; Bowen, D. T.; Crocker, P. R. Analysis of the CD33-related siglec family reveals that Siglec-9 is an endocytic receptor expressed on subsets of acute myeloid leukemia cells and absent from normal hematopoietic progenitors. Leuk. Res. 2007, 31, 211-220.
. Bradshaw, E. M.; Chibnik, L. B.; Keenan, B. T.; Ottoboni, L.; Raj, T.; Tang, A.; Rosenkrantz, L. L.; Imboywa, S.; Lee, M.; Von Korff, A.; The Alzheimer Disease Neuroimaging Initiative; Morris, M. C.; Evans, D. A.; Johnson, K.; Sperling, R. A.; Schneider, J. A.; Bennett, D. A.; De Jager, P. L. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nat. Neurosci. 2013, 16, 848-850.
. Avril, T.; Wagner, E. R.; Wilson, H. J.; Crocker, P. R. Sialic acid-binding immunoglobulin-like lectin 7 mediates selective recognition of sialylated glycans expressed on Campylobacter jejuni lipooligosaccharides. Infect. Immun. 2006, 74, 4133-4141.
. Jandus, C.; Boligan, K. F.; Chijoke, O.; Liu, H.; Dahlhaus, M.; Demoulins, T.; Schneider, C.; Wehrli, M.; Hunger, R. E.; Baelocher, G. M.; Simon, H. U.; Romero, P.; Munz, C.; von Gunten, S. Interactions between Siglec-7/9 receptors and ligands influence NK cell–dependent tumor immunosurveillance. J. Clin. Invest. 2014, 124, 1810-1820.
. Ernst, B.; Magnani, J. L. From carbohydrate leads to glycomimetic drugs. Nat. Rev Drug Discov. 2009, 8, 661-677.
. Filbin, M. T. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat. Rev. Neurosci. 2003, 4, 703-713.
. Vyas, A. A.; Blixt, O.; Paulson, J. C.; Schnaar, R. L. Potent glycan inhibitors of myelin-associated glycoprotein enhance axon outgrowth in Vitro. J. Biol. Chem. 2005, 280, 16305-16310.
. Yang, L. J.; Zeller, C. B.; Shaper, N. L.; Kiso, M.; Hasegawa, A.; Shapiro, R. E.; Schnaar, R. L. Gangliosides are neuronal ligands for myelin-associated glycoprotein. Proc. Natl. Acad. Sci. USA 1996, 93, 814-818.
. Shin, S. Y.; Gathje, H.; Schwardt, O.; Gao, G. P.; Ernst, B.; Kelm, S.; Meyer, B. Binding epitopes of gangliosides to their neuronal receptor, myelin-associated glycoprotein, from saturation transfer difference NMR. Chembiochem. 2008, 9, 2946-2949.
. Gao, G.; Smiesko, M.; Schwardt, O.; Gathje, H.; Kelm, S.; Vedani, A.; Ernst, B. Mimetics of the tri- and tetrasaccharide epitopes of GQ1b as myelin-associated glycoprotein (MAG) ligands. Bioorg. Med. Chem. 2007, 15, 7459-7469.
. Nicoll, G.; Ni, J.; Liu, D.; Klenerman, P.; Munday, J.; Dubock, S.; Mattei, M. G.; Crocker, P. R. Identification and characterization of a novel siglec, Siglec-7, expressed by human natural killer cells and monocytes. J. Biol. Chem. 1999, 274, 34089-34095.
. Yamaji, T.; Teranishi, T.; Alphey, M. S.; Crocker, P. R.; Hashimoto, Y. A small region of the natural killer cell receptor, Siglec-7, ss responsible for its preferred binding to 2,8-disialyl and branched 2,6-sialyl residues: A comparison with Siglec-9. J. Biol. Chem. 2002, 277, 6324-6332.
. Angata, T.; Hayakawa, T.; Yamanaka, M.; Varki, A.; Nakamura, M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. FASEB J. 2006, 20, 1964-1973.
. Angata, T.; Ishii, T.; Motegi, T.; Oka, R.; Taylor, R. E.; Soto, P. C.; Chang, Y. C.; Secundino, I.; Gao, C. X.; Ohtsubo, K.; Kitazume, S.; Nizet, V.; Varki, A.; Gemma, A.; Kida, K.; Taniguchi, N. Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell. Mol. Life. Sci. 2013, 70, 3199-3210.
. Angata, T.; Tabuchi, Y.; Nakamura, K.; Nakamura, M. Siglec-15: an immune system Siglec conserved throughout vertebrate evolution. Glycobiology 2007, 17, 838-846.
. Takamiya, R.; Ohtsubo, K.; Takamatsu, S.; Taniguchi, N.; Angata, T. The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12–Syk pathway. Glycobiology 2013, 23, 178-187.
. 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 2,6-sialyltransferase. J. Am. Soc. Chem. 2013, 135, 18280-18283.
. Chien, W. T.; Liang, C. F.; Yu, C. C.; Lin, C. H.; Li, S. P.; Premadona, I.; Chen, Y. J.; Mong, K. K.; Lin, C. C. Sequential one-pot enzymatic synthesis of oligo-N-acetyllactosamine and its multi-sialylated extensions. Chem. Comm. 2014, 50, 5786-5789.
. 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, 5205-5208.
. Takakura, H.; Kojima, R.; Urano, Y.; Terai, T.; Hanaoka, K.; Nagano, T. Aminoluciferins as functional bioluminogenic substrates of firefly luciferase. Chem. Asian J. 2011, 6, 1800-1810.
. Martins-Teixeira, M. B.; Campo, V. L.; Biondo, M.; Sesti-Costa, R.; Carneiro, Z. A.; Silva, J. S.; Carvohol, I. -Selective glycosylation affords mucin-related GalNAc amino acids and diketopiperazines active on Trypanosoma cruzi. Bioorg. Med. Chem. 2013, 21, 1978-1987.
. 陳仲宇，國立清華大學化學研究所，碩士論文，腫瘤相關抗原Globo-H 與SSEA-3之合成研究，民國98年

全文公開日期本全文未授權公開 (校內網路)
全文公開日期本全文未授權公開 (校外網路)

簡易檢索 / 詳目顯示

相關論文