臺灣博碩士論文加值系統

醣基化是描述連結醣基到受質分子並形成糖苷鍵的化學反應。受質分子可能是小分子,例如另一個醣分子；或者是巨大分子,例如蛋白質。醣基化會改變受質分子的物理特性,化學特性或生物特性。因此醣基化與許多研究領域，例如:細胞識別，疾病發生，藥物研發，藥物代謝，抗生素抗藥性和xenobiotic的去毒性均有密切關係。根據形成醣苷鍵的橋接元素,可將醣基化分成氧、硫、氮和碳等不同的醣基化反應形式。
在本篇研究中，我們發現了來自枯草桿菌(Bacillus cereus)的轉醣酶BcGT1能將醣基自UDP-gluocose (尿苷二磷酸葡萄糖) 轉移到多種受質分子上，展現了廣泛的受質多樣性。超過20種結構迥異的化學分子均可被BcGT1醣基化。根據這些分子的結構，可歸納出BcGT1醣基化反應的幾種特性。 (1) 醣基受質分子必須至少含有一個苯環，可以是多環或單環系統，也可以是雜環系統。(2) 與醣基發生接合反應的醇基，硫醇基或胺基不一定要直接接在苯環上。胺基可以是一級、二級或三級胺。(3) 超過一個醣基可以被接到受質上，醣鏈長度取決於受質的特性。
為進一步確認BcGT1的產物結構，我們挑選了4種醣基受質 (Fluorescein methyl ester, 17-β-estradiol, 7-mercapto-4-methylcoumarin and 6-benzylaminopurine) 分別代表了氧、硫及氮醣基化反應，用BcGT1進行醣基化並將產物純化後用MS及NMR進行結構分析。所有的產物均為β構型證實了BcGT1確實為inverting enzyme。此結果不僅證實了BcGT1的受質多樣性，亦顯示了BcGT1未來應用於高價值、具生物活性分子的醣基化生物轉化反應的潛力。
此外，本研究亦根據BcGT1結晶結構資訊進行突變分析。為了解活性區的胺基酸殘基對酵素反應性的影響，我們將位於活性區(active site)的10個胺基酸突變成alanine, 形成E12A, H14A, D106A, H108A, T238A, F240A, N306A, E310A, D326A, Q327A等10株突變株。在以槲皮素(quercetin)為醣基受質的反應中,我們發現T238A、E310A和D326A對反應性有嚴重的影響，反應性分別降為野生株的24 %， 0 %及0 %。對照結晶結構發現T238負責固定UDP (尿苷二磷酸) 上的phosphate，E310負責固定UDP上的ribose。另外，雖然glucose的binding site未能從結晶結構上看出,然而比對其他轉醣酵素的基因序列發現D326可能擔負UDP-glucose上glucose的固定。顯示UDP-glucose的固定對於酵素反應的進行十分重要。另外，從產物接醣位向的分析亦得知T238A、F240A、N306A 和Q327A對醣基化位向的選擇性與野生株有顯著不同，其中最值得注意的是F240A，從結晶結構得知F240位於quercetin binding site，並以苯環與quercetin交互作用。從產物位向分析結果亦進一步證實F240能影響醣基化位向，其控制位向的機制為何?值得進一步研究。
為了解F240如何控制產物位向，我們將F240置換成一系列化性迥異的胺基酸，例如C，E，G，R，Y，W和K，形成一系列的突變株。其中F240A、F240G、F240R 和F240K 明顯改變了酵素的位向選擇性。在此四個突變株中最主要的產物是3-O-(β-D-glucopyranosyl)-quercetin，野生株則主要產生7-O-(β-D-glucopyranosyl)-quercetin。其中F240R呈現幾乎100 % 位向選擇性，但是活性只有野生株的25 %。從X-ray結構觀測，我們得知除F240之外，另有兩個胺基酸, F132和F138與F240共同形成非極性的受質鍵結區，可容納含芳香環的受質。將F置換成Y可能可以增加氫鍵的作用力更進一步穩定受質。因此我們進一步建立了F240R_F132Y，F240R_F138Y 和F240R_F132Y_F138Y等多重突變株。這些多重突變株不只保持了F240R的高選擇性，並進一步改進了F240R的酵素活性，可適用於其它黃酮類受質如山奈酚 (kaempferol) 及楊梅黃酮 (myricetin)等。
為進一步降低反應的成本，我們亦考慮了UDP的回收。來自豆類Pisum sativum的sucrose synthase基因被放在E. coli中表現，但呈現不可溶的形態。將其作refolding後恢復了活性，並能夠催化UDP的再生。然而再摺疊的試劑昂貴，因此考慮另一來源自藍綠菌Anabaena CH3的sucrose synthase。在E. coli表現後，發現約有一半為不可溶形態，自其中回收有活性酵素的實驗尚未成功。因此有效再生UDP-glucose的方法仍待後續研究。將帶有BcGT1基因的大腸桿菌作為細胞反應器，利用大腸桿菌進行細胞壁合成時本身所產生的UDP-glucose作為BcGT1的反應物, 或許是未來可以嘗試的作法。

Glycosylation is a process of connecting a carbohydrate to an acceptor and forming a glycosidic bond. The acceptor can be a small molecule such as sugar, or a macromolecule such as protein. Glycosylation can alter the physical, chemical and biological functions of acceptors. Hence glycosylation is highly correlated to many research fields such as cell-cell recognition, disease development, drug discovery, drug metabolism, antibiotics resistance, and xenobiotics detoxification. According to the bridge atom in glycosidic bond, glycosylation can be divided into several types like O-glycosylation, S-glycosylation, N-glycosylation, and C-glycosylation.
In this research, we found that glycosyltransferase 1 from Bacillus cereus (BcGT1) catalyzed the transfer of a glucosyl moiety from uridine diphosphate glucose (UDP-glucose) to various acceptors. The specificity of acceptors was found to be broad: more than 20 compounds classified into O-, S-, and N-linkage glucosides could be prepared by BcGT1 catalysis. Based on this work, some features of BcGT1 reaction could be summarized as follows. (1) The acceptors should contain at least one aromatic ring system. Fused rings or heteroaromatic ring systems were also valid, too. (2) The nucleophilic groups of acceptors could be -OH, -SH, -NH2, -NRH or -NR2 moiety directly attached to the aromatic ring or through an aliphatic spacer. (3) More than one glucose unit could be transferred from UDP-glucose to acceptors. The length of glucose chain largely depended on the nature of substrates.
Besides, four representative acceptors - fluorescein methyl ester, 17-β-estradiol, 7-mercapto-4-methylcoumarin, and 6-benzylaminopurine - were chosen as a candidate acceptor for O-, S-, and N-glucosylation, respectively. These enzymatic products were purified and the structures were elucidated by MS and NMR spectra. As all isolated glucosides were β-anomers, BcGT1 was confirmed to be an inverting enzyme. This study not only demonstrated the substrate promiscuity of BcGT1 but also showed the great application prospect of this enzyme in bioconversion of valuable bioactive molecules.
In addition, we also carried out mutagenesis analysis according to the detail x-ray structure of BcGT1. In order to understand the effect of amino acid residues in the active site, 10 single point mutants (E12A, H14A, D106A, H108A, T238A, F240A, N306A, E310A, D326A, and Q327A) of BcGT1 were prepared by site-directed mutagenesis. In the glucosylation of quercetin, we found that T238A, E310A and D326A showed serious decrease in enzymatic activity. The activities of these three mutants became 24 %, 0 %, and 0 % respectively relative to wild type strain. From the X-ray structure of BcGT1, T238 and E310 are suggested to be responsible for the stabilization of phosphate and ribose groups of uridine diphosphate (UDP). D326 is suggested to be responsible for the glucose stabilization from sequence alignment with other glycosyltransferase. Based on the information above, we propose that the UDP-glucose stabilization was critical to BcGT1 activity. On the other hand, the regioselectivity of T238A, F240A, N306A, and Q327A were significantly different from wild type strain. The most significant change was observed in F240A. From X-ray structure, we knew that F240 was located in the substrate binding site and stabilized quercetin via benzene ring. From the regioselectivity analysis, F240 was further proved to be able to affect the resioselectivity of quercetin glucosylation. The detail mechanism of regioselectivity controlling needs to be further studied.
To unveil and further to control the catalytic function of BcGT1, mutation of F240 to other amino acids, such as C, E, G, R, Y, W, and K, was performed. Among these mutants, F240A, F240G, F240R, and F240K greatly altered their regioselectivity. The 3-O-(β-D-glucopyranosyl)-quercetin, instead of 7-O-(β-D-glucopyranosyl)-quercetin as for the wild-type enzyme, was obtained as the major product. Among these mutants, F240R showed nearly 100 % product specificity, but only retained 25 % catalytic efficiency of wild type enzyme. From an inspection of the protein structure, we find two other amino acids, F132 and F138, together with F240, are likely to form a hydrophobic binding region, which is sufficiently spacious to accommodate substrates with varied aromatic moieties. Through the replacement of a phenylalanine by a tyrosine residue in the substrate-binding region, the mutants may be able to fix the orientation of flavonoids, presumably through the formation of a hydrogen bond between substrate and mutants. Multiple mutants - F240R_F132Y, F240R_F138Y and F240R_F132Y_F138Y - were thus constructed for further investigation. The multiple points of mutants not only maintained the high product specificity but also significantly improved the catalytic efficiency, relative to F240R. The same product specificity was obtained when kaempferol and myricetin were used as a substrate.
Finally, in order to decrease the cost of BcGT1 reaction, UDP-glucose regeneration system was also considered. Sucrose synthases (SUS) derived from Pisum sativum (pea) was heterogeneous expressed in E. coli. However, it was in an insoluble form. The refolding of enzyme was successful, and the refolded enzyme was demonstrated to be capable to catalyze the regeneration of UDP-glucose. However, the refolding reagent was expensive, and therefore another source, the SUS from Anabaena CH3, was considered. This enzyme was about 50 % in soluble form when expressed in E. coli. An optimum enzyme purification process was not established yet. Hence an effective UDP-glucose regeneration system was still left for further study in the future. Perhaps the whole cell bioreactor which uses the UDP-glucose generated when cell wall synthesis is carried out in E. coli could be a possible solution.

中文摘要 I
ABSTRACT III
致謝 VI
INDEX VII
FIGURE INDEX XII
TABLE INDEX XIV
1. INTRODUCTION 1
1.1 GLYCOSYLATION AND GLYCOSIDE 1
1.1.1 Glycosylation, glucosylation and glucosidation 1
1.1.2 Importance of glycosylation 1
1.1.3 Benefits of using glycoside as prodrugs 3
1.1.4 Classification of glycosylation 4
1.1.5 Methods to carry out glycosylation 4
1.2 GLYCOSYLTRANSFERASES (GTS) 5
1.2.1 Classification of GTs 5
1.2.2 Structures of GTs 5
1.2.3 Reaction mechanisms of GTs 7
1.2.4 Substrate diversity of GTs 8
1.2.5 Regioselectivity of GTs 9
1.2.6 BcGT1 from Bacillus cereus 11
1.3 BIOACTIVE COMPOUNDS USED IN THIS STUDY 13
1.3.1 Curcumin (薑黃素) 13
1.3.2 Fluorescein methyl ester 14
1.3.3 17-β-estradiol (雌二醇) 14
1.3.4 Harmalol (駱駝蓬酚) and harmine (駱駝蓬鹼) 15
1.3.5 Honokiol (和厚樸酚) and magnolol (厚樸酚) 16
1.3.6 Hydroquinone 16
1.3.7 4-Methyl-7-hydroxyl coumarin and 7-mercapto-4-methyl coumarin (香豆素衍生物) 17
1.3.8 Quercetin (槲皮素) 17
1.3.9 Resveratrol (白藜蘆醇) 19
1.3.10 6-Benzylaminopurine 20
1.3.11 Diclofenac 21
1.3.12 Imipramine 21
1.3.13 Indirubin (靛玉紅) 22
1.3.14 Kaempferol (山奈酚) 22
1.3.15 Myricetin (楊梅黃酮) 23
1.3.16 BPR2P0064S0 23
1.4 UDP-GLUCOSE REGENERATION SYSTEM 24
1.4.1 Regeneration of UDP-glucose 24
1.4.2 Sucrose synthase (SUS) 26
1.5 PURPOSE OF THIS STUDY 30
2. METHODS 31
2.1 CONSTRUCTION OF BCGT1 PLASMID AND PURIFICATION OF RECOMBINANT BCGT1 31
2.1.1 Construction of BcGT1_pRSETA plasmid 31
2.1.2 Purification of recombinant BcGT1 32
2.2 SUBSTRATE DIVERSITY AND GLUCOSYLATION PRODUCTS ISOLATION 32
2.2.1 Glucosylation and LC-MS-MS analysis 32
2.2.2 Fluorescein methyl ester glucosylation product identification 33
2.2.3 17-β-estradiol glucosylation product identification 33
2.2.4 7-Mercapto-4-methylcoumarin glucosylation product identification 34
2.2.5 6-Benzylaminopurine glucosylation product identification 35
2.3 X-RAY STRUCTURE OF BCGT1 AND MUTATION STUDY 36
2.3.1 X-ray structure determination 36
2.3.2 Site-directed mutagenesis of BcGT1 36
2.3.3 Glucosylation of quercetin and regioselectivity analysis 37
2.3.4 Substrate diversity of mutant enzymes 38
2.4 REGIOSELECTIVITY OF BCGT1 TOWARD FLAVONOIDS 38
2.4.1 Primers design of BcGT1 in flavonoids regioselective glucosylation study 38
2.4.2 Glucosylation, product identification, and regioselectivity analysis of quercetin 39
2.4.3 Glucosylation, product identification, and regioselectivity analysis of kaempferol 40
2.4.4 Glucosylation, product identification, and regioselectivity analysis of myricetin 41
2.4.5 Molecular docking 42
2.5 UDP-GLUCOSE REGENERATION SYSTEM DEVELOPMENT 42
2.5.1 Plasmid construction and expression of SUS from Pisum sativum (Pea) 42
2.5.2 Coupling of BcGT1 and SUS_Pea 43
2.5.3 Cloning and expression of SUS from Anabaena CH3 43
3. RESULTS AND DISCUSSION 48
3.1 OVER EXPRESSION AND PURIFICATION OF BCGT1 48
3.1.1 Construction of expression plasmid of BcGT1 48
3.1.2 Over expression of BcGT1 in E. coli 49
3.2 SUBSTRATE DIVERSITY OF BCGT1 50
3.2.1 Diversity of substrates used by BcGT1 50
3.2.2 Identification of product of fluorescein methyl ester 54
3.2.3 Identification of product of 17-β-estradiol 56
3.2.4 Identification of product of 7-mercapto-4-methylcoumarin 59
3.2.5 Identification of product of 6-benzylaminopurine 61
3.3 PROTEIN STRUCTURE OF BCGT1 AND MUTATION STUDY 64
3.3.1 Protein structure of BcGT1 64
3.3.2 Mutagenesis study of amino acid residues in active site of BcGT1 66
3.4 REGIOSELECTIVITY OF BCGT1 TOWARD FLAVONOIDS 74
3.4.1 Identification of quercetin monoglucosides 74
3.4.2 Product amount and regioselectivity of BcGT1 mutants toward quercetin 77
3.4.3 Product amount and regioselectivity of BcGT1 mutant toward kaempferol 81
3.4.4 Product amount and regioselectivity of BcGT1 mutant toward myricetin 85
3.4.5 Explanation of the high regioselectivity of BcGT1 mutants by molecular docking 89
3.5 UDP-GLUCOSE REGENERATION SYSTEM 90
3.5.1 Expression of SUS1 from Pisum sativum (pea) 90
3.5.2 Coupling of BcGT1 and SUS from pea 92
3.5.3 Cloning and expression of SUS from Anabaena CH3 94
4. CONCLUSIONS 105
5. FURTHER STUDY 108
5.1 UNIVERSAL GLUCOSYLATION KIT FOR AROMATIC COMPOUNDS 108
5.2 GLYCOSIDATION AS A POTENTIAL DRUG DELIVERY TOOL THROUGH TARGETING TO GLUCOSE TRANSPORTER ON CELL MEMBRANE 109
5.3 UNIVERSAL QUANTITATIVE METHOD DEVELOPMENT FOR GLYCOSYLTRANSFERASE ACTIVITY 110
5.4 WHOLE CELL AS A GLUCOSYLATION BIOREACTOR 111
6. REFERENCES 112
7. APPENDIX 125
APPENDIX 1 125
APPENDIX 2 126
APPENDIX 3-1 129
APPENDIX 3-2 130
APPENDIX 3-3 131
APPENDIX 3-4 132
APPENDIX 4-1 133
APPENDIX 4-2 134
APPENDIX 4-3 135
APPENDIX 4-4 136
APPENDIX 4-5 137
APPENDIX 4-6 138
APPENDIX 4-7 139
APPENDIX 5-1 140
APPENDIX 5-2 141
APPENDIX 5-3 142
APPENDIX 6-1 143
APPENDIX 6-2 144
APPENDIX 6-3 145
APPENDIX 7 146
APPENDIX 8-1 147
APPENDIX 8-2 148
APPENDIX 8-3 149
APPENDIX 8-4 150
APPENDIX 8-5 151
APPENDIX 8-6 152
APPENDIX 9 153
APPENDIX 10 155
APPENDIX 11-1 158
APPENDIX 11-2 159
APPENDIX 11-3 160
APPENDIX 11-4 162
APPENDIX 11-5 163
APPENDIX 11-6 166

[1] Guimaraes, A. M., Stapleton, P., Ji, X., Oliyide, A., Osbourn, A., Pandit, S., Bowles, D., Davis, B., Schatzlein, A., and Yang, M. (2011) Glycosylation enhances selectivity of novobiocin and alters antibacterial mechanism, In Abstract of Papers of the American Chemical Society.
[2] Gachon, C. M., Langlois-Meurinne, M., and Saindrenan, P. (2005) Plant secondary metabolism glycosyltransferases: the emerging functional analysis, Trends Plant Sci. 10, 542-549.
[3] Zelder, F., and Tivana, L. (2015) Corrin-based chemosensors for the ASSURED detection of endogenous cyanide, Organic & biomolecular chemistry 13, 14-17.
[4] Shimoda, K., Kubota, N., Taniuchi, K., Sato, D., Nakajima, N., Hamada, H., and Hamada, H. (2010) Biotransformation of naringin and naringenin by cultured Eucalyptus perriniana cells, Phytochemistry 71, 201-205.
[5] Wright, G. D. (2005) Bacterial resistance to antibiotics: enzymatic degradation and modification, Adv Drug Deliv Rev 57, 1451-1470.
[6] Rowland, A., Miners, J. O., and Mackenzie, P. I. (2013) The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification, The international journal of biochemistry & cell biology 45, 1121-1132.
[7] Margraf-Schonfeld, S., Bohm, C., and Watzl, C. (2011) Glycosylation affects ligand binding and function of the activating natural killer cell receptor 2B4 (CD244) protein, J. Biol. Chem. 286, 24142-24149.
[8] Jaeken, J., and Matthijs, G. (2007) Congenital disorders of glycosylation: a rapidly expanding disease family, Annu Rev Genomics Hum Genet 8, 261-278.
[9] Friend, D. R., and Chang, G. W. (1984) A colon-specific drug-delivery system based on drug glycosides and the glycosidases of colonic bacteria, J. Med. Chem. 27, 261-266.
[10] Sinha, V., and Kumria, R. (2001) Colonic drug delivery: prodrug approach, Pharm. Res. 18, 557-564.
[11] Nag, S. A., Qin, J., Wang, W., Wang, M.-H., Wang, H., and Zhang, R. (2012) Ginsenosides as anticancer agents: in vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action, Front. Pharmacol. 3, 25.
[12] Oliveira-Brett, A. M., and Diculescu, V. C. (2004) Electrochemical study of quercetin–DNA interactions: Part II. In situ sensing with DNA biosensors, Bioelectrochemistry 64, 143-150.
[13] Kawabata, Y., Wada, K., Nakatani, M., Yamada, S., and Onoue, S. (2011) Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications, Int. J. Pharm. 420, 1-10.
[14] Zhang, J. A., Anyarambhatla, G., Ma, L., Ugwu, S., Xuan, T., Sardone, T., and Ahmad, I. (2005) Development and characterization of a novel Cremophor® EL free liposome-based paclitaxel (LEP-ETU) formulation, Eur. J. Pharm. Biopharm. 59, 177-187.
[15] Morand, C., Manach, C., Crespy, V., and Remesy, C. (2000) Quercetin 3-O-β-glucoside is better absorbed than other quercetin forms and is not present in rat plasma, Free Radic. Res. 33, 667-676.
[16] de Graaf, M., Pinedo, H. M., Quadir, R., Haisma, H. J., and Boven, E. (2003) Cytosolic β-glycosidases for activation of glycoside prodrugs of daunorubicin, Biochem. Pharmacol. 65, 1875-1881.
[17] Nolen, H., 3rd, Fedorak, R., and Frient, D. (1995) Budesonide‐β‐D‐glucuronide: A potential prodrug for treatment of ulcerative colitis, J. Pharm. Sci. 84, 677-681.
[18] Fedorak, R. N., Haeberlin, B., Empey, L. R., Cui, N., Nolen, H., Jewell, L. D., and Friend, D. R. (1995) Colonic delivery of dexamethasone from a prodrug accelerates healing of colitis in rats without adrenal suppression, Gastroenterology 108, 1688-1699.
[19] Panda, S., and Kar, A. (2007) Antidiabetic and antioxidative effects of Annona squamosa leaves are possibly mediated through quercetin-3-O-glucoside, BioFactors 31, 201-210.
[20] Ke, M., Hu, X.-Q., Ouyang, J., Dai, B., and Xu, Y. (2012) The effect of astragalin on the VEGF production of cultured Müller cells under high glucose conditions, Bio-Med. Mater. Eng. 22, 113-119.
[21] Day, A. J., Gee, J. M., DuPont, M. S., Johnson, I. T., and Williamson, G. (2003) Absorption of quercetin-3-glucoside and quercetin-4'-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter, Biochem. Pharmacol. 65, 1199-1206.
[22] Bai, Y., Mao, Q. Q., Qin, J., Zheng, X. Y., Wang, Y. B., Yang, K., Shen, H. F., and Xie, L. P. (2010) Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo, Cancer Sci. 101, 488-493.
[23] Razavi, S. M., Zahri, S., Zarrini, G., Nazemiyeh, H., and Mohammadi, S. (2009) Biological activity of quercetin-3-O-glucoside, a known plant flavonoid, Bioorganicheskaia khimiia 35, 414-416.
[24] Discher, S., Burse, A., Tolzin-Banasch, K., Heinemann, S. H., Pasteels, J. M., and Boland, W. (2009) A versatile transport network for sequestering and excreting plant glycosides in leaf beetles provides an evolutionary flexible defense strategy, ChemBioChem 10, 2223-2229.
[25] Shipkova, M., Armstrong, V. W., Oellerich, M., and Wieland, E. (2003) Acyl glucuronide drug metabolites: toxicological and analytical implications, Ther. Drug Monit. 25, 1-16.
[26] Yang, F., Lian, G., and Yu, B. (2010) Synthesis of raphanuside, an unusual oxathiane-fused thioglucoside isolated from the seeds of Raphanus sativus L, Carbohydr. Res. 345, 309-314.
[27] Jaki, B., Sticher, O., Veit, M., Fröhlich, R., and Pauli, G. F. (2002) Evaluation of glucoiberin reference material from Iberis amara by spectroscopic fingerprinting, J. Nat. Prod. 65, 517-522.
[28] Šardzík, R., Both, P., and Flitsch, S. L. (2011) Post-translational modifications: S-linked sugars lost and found, Nat. Chem. Biol. 7, 69-70.
[29] Gao, Y., Zhao, G., Liu, W., Wang, Y., Xu, W., and Wang, J. (2010) Thiadiazole‐based thioglycosides as sodium‐glucose co‐transporter 2 (SGLT2) inhibitors, Chin. J. Chem . 28, 605-612.
[30] Hirohara, S., Obata, M., Alitomo, H., Sharyo, K., Ando, T., Tanihara, M., and Yano, S. (2009) Synthesis, photophysical properties and sugar-dependent in vitro photocytotoxicity of pyrrolidine-fused chlorins bearing S-glycosides, J. Photochem. Photobiol. B 97, 22-33.
[31] MacDougall, J. M., Zhang, X. D., Polgar, W. E., Khroyan, T. V., Toll, L., and Cashman, J. R. (2004) Design, chemical synthesis, and biological evaluation of thiosaccharide analogues of morphine- and codeine-6-glucuronide, J. Med. Chem. 47, 5809-5815.
[32] Mohorko, E., Glockshuber, R., and Aebi, M. (2011) Oligosaccharyltransferase: the central enzyme of N-linked protein glycosylation, J. Inherit. Metab. Dis. 34, 869-878.
[33] Lu, C., Bai, L., and Shen, Y. (2004) A novel amide N-glycoside of ansamitocins from Actinosynnema pretiosum, J. Antibiot. (Tokyo) 57, 348-350.
[34] Wang, W., Rattananakin, P., and Goekjian, P. G. (2003) Synthesis of N‐glycoside analogs via thionolactones, J. Carbohydr. Chem. 22, 743-751.
[35] Eichholzer, J., MacLeod, J., and Summons, R. (1978) Studies of the thermal N 3 to N 9 rearrangement of the 3-β-D-Glucoside of the cytokinin, 6-benzylaminopurine, Aust. J. Chem. 31, 893-899.
[36] Nandi, V., and Soine, W. H. (1997) HPLC analysis for amobarbital N-glycosides in urine, J. Pharm. Biomed. Anal. 15, 1187-1195.
[37] Tawara, J. N., Johnston, J. J., and Goodall, M. J. (1996) Degradation of 3-chloro-p-toluidine hydrochloride in watermelon bait. Identification and chemical characterization of novel N-glucoside and oxopropanimine, J. Agric. Food Chem. 44, 3983-3988.
[38] Martin, G. D., Tan, L. T., Jensen, P. R., Dimayuga, R. E., Fairchild, C. R., Raventos-Suarez, C., and Fenical, W. (2007) Marmycins A and B, cytotoxic pentacyclic C-glycosides from a marine sediment-derived actinomycete related to the genus Streptomyces, J. Nat. Prod. 70, 1406-1409.
[39] Nomura, S., Sakamaki, S., Hongu, M., Kawanishi, E., Koga, Y., Sakamoto, T., Yamamoto, Y., Ueta, K., Kimata, H., and Nakayama, K. (2010) Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, J. Med. Chem. 53, 6355-6360.
[40] Mydock, L. K., and Demchenko, A. V. (2010) Mechanism of chemical O-glycosylation: from early studies to recent discoveries, Org Biomol Chem 8, 497-510.
[41] Van Den Broek, L. A., and Voragen, A. G. (2008) Bifidobacterium glycoside hydrolases and (potential) prebiotics, Innovative Food Science & Emerging Technologies 9, 401-407.
[42] Zhou, M., and Thorson, J. S. (2011) Asymmetric enzymatic glycosylation of mitoxantrone, Org. Lett. 13, 2786-2788.
[43] Jung, C. M., Heinze, T. M., Schnackenberg, L. K., Mullis, L. B., Elkins, S. A., Elkins, C. A., Steele, R. S., and Sutherland, J. B. (2009) Interaction of dietary resveratrol with animal‐associated bacteria, FEMS Microbiol. Lett. 297, 266-273.
[44] Aumiller, J. J., Mabashi-Asazuma, H., Hillar, A., Shi, X., and Jarvis, D. L. (2012) A new glycoengineered insect cell line with an inducibly mammalianized protein N-glycosylation pathway, Glycobiology 22, 417-428.
[45] Buchheit, D., Dragan, C. A., Schmitt, E. I., and Bureik, M. (2011) Production of ibuprofen acyl glucosides by human UGT2B7, Drug Metab. Dispos. 39, 2174-2181.
[46] Campbell, J. A., Davies, G. J., Bulone, V., and Henrissat, B. (1997) A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities, Biochem. J. 326, 929.
[47] Breton, C., Fournel-Gigleux, S., and Palcic, M. M. (2012) Recent structures, evolution and mechanisms of glycosyltransferases, Curr. Opin. Struct. Biol. 22, 540-549.
[48] Lairson, L., Henrissat, B., Davies, G., and Withers, S. (2008) Glycosyltransferases: structures, functions, and mechanisms, Biochemistry 77, 521.
[49] Kudo, F., Kasama, Y., Hirayama, T., and Eguchi, T. (2007) Cloning of the pactamycin biosynthetic gene cluster and characterization of a crucial glycosyltransferase prior to a unique cyclopentane ring formation, The Journal of antibiotics 60, 492-503.
[50] Mulichak, A. M., Losey, H. C., Walsh, C. T., and Garavito, R. M. (2001) Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide aglycone in the biosynthesis of vancomycin group antibiotics, Structure 9, 547-557.
[51] Wang, H., and van der Donk, W. A. (2011) Substrate selectivity of the sublancin S-glycosyltransferase, J. Am. Chem. Soc. 133, 16394-16397.
[52] Green, M. D., King, C. D., Mojarrabi, B., Mackenzie, P. I., and Tephly, T. R. (1998) Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3, Drug Metab. Disposition 26, 507-512.
[53] Gantt, R. W., Goff, R. D., Williams, G. J., and Thorson, J. S. (2008) Probing the aglycon promiscuity of an engineered glycosyltransferase, Angew. Chem. Int. Ed. Engl. 47, 8889-8892.
[54] Wang, X. (2009) Structure, mechanism and engineering of plant natural product glycosyltransferases, FEBS Lett. 583, 3303-3309.
[55] Itaaho, K., Uutela, P., Kostiainen, R., Radominska-Pandya, A., and Finel, M. (2008) Dopamine is a low affinity and high specificity substrate for the human UDP-glucuronosyltransferase 1A10, Drug Metab. Disposition.
[56] Dubois, S. G., Beaulieu, M., Lévesque, É., Hum, D. W., and Bélanger, A. (1999) Alteration of human UDP-glucuronosyltransferase UGT2B17 regio-specificity by a single amino acid substitution, J. Mol. Biol. 289, 29-39.
[57] Lim, E. K., Ashford, D. A., Hou, B., Jackson, R. G., and Bowles, D. J. (2004) Arabidopsis glycosyltransferases as biocatalysts in fermentation for regioselective synthesis of diverse quercetin glucosides, Biotechnol. Bioeng. 87, 623-631.
[58] Hyung Ko, J., Gyu Kim, B., and Joong-Hoon, A. (2006) Glycosylation of flavonoids with a glycosyltransferase from Bacillus cereus, FEMS Microbiol. Lett. 258, 263-268.
[59] Ahn, J. H., Chong, Y. H., Joe, E. J., and Ri, J. N. (2010) Change of Bacillus cereus flavonoid O-triglucosyltransferase into flavonoid O-monoglucosyltransferase by error-prone polymerase chain reaction, Journal of microbiology and biotechnology 20, 1393-1396.
[60] Cheng, A.-L., Hsu, C.-H., Lin, J.-K., Hsu, M.-M., Ho, Y.-F., Shen, T.-S., Ko, J.-Y., Lin, J.-T., Lin, B.-R., and Ming-Shiang, W. (2000) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions, Anticancer Res. 21, 2895-2900.
[61] Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., and Frautschy, S. A. (2005) Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo, J. Biol. Chem. 280, 5892-5901.
[62] Parvathy, K., Negi, P., and Srinivas, P. (2009) Antioxidant, antimutagenic and antibacterial activities of curcumin-β-diglucoside, Food Chem. 115, 265-271.
[63] Shrikanth Gadad, B., K Subramanya, P., Pullabhatla, S., S Shantharam, I., and KS, R. (2012) Curcumin-glucoside, a novel synthetic derivative of curcumin, inhibits α-synuclein oligomer formation: relevance to Parkinson's disease, Curr. Pharm. Des. 18, 76-84.
[64] Stege, P. W., Messina, G. A., Bianchi, G., and Olsina, R. A. (2010) Determination of the β-glucosidase activity in different soils by pre capillary enzyme assay using capillary electrophoresis with laser-induced fluorescence detection, Journal of fluorescence 20, 517-523.
[65] Burke, D. G., Heales, S. J., and Vellodi, A. (2015) Lysosomal β-glucosidase (GBA1) and non-lysosomal β-glucosidase (GBA2): Potential involvement in the pathogenesis of Gaucher disease/Parkinson disease, Mol. Genet. Metab. 114, S26.
[66] Sweeney, A. T., Tangpricha, V., Weinberg, J., Malabanan, A. O., Chimeh, F. N., and Holick, M. F. (2006) Comparison of the effects of a new conjugated oral estrogen, estradiol-3-beta-glucoside, with oral micronized 17-beta-estradiol in postmenopausal women, Transl. Res. 148, 164-170.
[67] Kim, H., Sablin, S. O., and Ramsay, R. R. (1997) Inhibition of monoamine oxidase A by β-carboline derivatives, Arch. Biochem. Biophys. 337, 137-142.
[68] Lee, C. S., Han, E. S., Jang, Y. Y., Han, J. H., Ha, H. W., and Kim, D. E. (2000) Protective effect of harmalol and harmaline on MPTP neurotoxicity in the mouse and dopamine‐induced damage of brain mitochondria and PC12 cells, J. Neurochem. 75, 521-531.
[69] Cho, J. H., Jeon, Y.-J., Park, S.-M., Shin, J.-C., Lee, T.-H., Jung, S., Park, H., Ryu, J., Chen, H., and Dong, Z. (2015) Multifunctional effects of honokiol as an anti-inflammatory and anti-cancer drug in human oral squamous cancer cells and xenograft, Biomaterials 53, 274-284.
[70] Ikeda, K., Sakai, Y., and Nagase, H. (2003) Inhibitory effect of magnolol on tumour metastasis in mice, Phytother. Res. 17, 933-937.
[71] Xu, Q., Yi, L.-T., Pan, Y., Wang, X., Li, Y.-C., Li, J.-M., Wang, C.-P., and Kong, L.-D. (2008) Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents, Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 715-725.
[72] Yang, L., Wang, Z., Lei, H., Chen, R., Wang, X., Peng, Y., and Dai, J. (2014) Neuroprotective glucosides of magnolol and honokiol from microbial-specific glycosylation, Tetrahedron 70, 8244-8251.
[73] Funayama, M., Arakawa, H., Yamamoto, R., Nishino, T., Shin, T., and Murao, S. (1995) Effects of α-and β-arbutin on activity of tyrosinases from mushroom and mouse melanoma, Biosci., Biotechnol., Biochem. 59, 143-144.
[74] Bae, E.-J., Yang, N. Y., Lee, C., Lee, H.-J., Kim, S., Sardi, S. P., and Lee, S.-J. (2015) Loss of glucocerebrosidase 1 activity causes lysosomal dysfunction and α-synuclein aggregation, Exp. Mol. Med. 47, e153.
[75] Lokeshwar, V. B., Lopez, L. E., Munoz, D., Chi, A., Shirodkar, S. P., Lokeshwar, S. D., Escudero, D. O., Dhir, N., and Altman, N. (2010) Antitumor activity of hyaluronic acid synthesis inhibitor 4-methylumbelliferone in prostate cancer cells, Cancer Res. 70, 2613-2623.
[76] Chen, Y., Zhou, J., Wang, H., Xia, Y., Yang, Z. Y., and Xia, P. (2008) Synthesis and anti-HBV activity of S-substituted 7-mercapto-4-methylcoumarin analogs, Chin. Chem. Lett. 19, 925-927.
[77] Thapa, M., Kim, Y., Desper, J., Chang, K.-O., and Hua, D. H. (2011) Synthesis and antiviral activity of substituted quercetins, Bioorganic & medicinal chemistry letters.
[78] Granado-Serrano, A. B., Martín, M. Á., Bravo, L., Goya, L., and Ramos, S. (2012) Quercetin attenuates TNF-induced inflammation in hepatic cells by inhibiting the NF-κB pathway, Nutr. Cancer 64, 588-598.
[79] Perez-Vizcaino, F., and Duarte, J. (2010) Flavonols and cardiovascular disease, Mol. Aspects Med. 31, 478-494.
[80] Spagnuolo, C., Russo, M., Bilotto, S., Tedesco, I., Laratta, B., and Russo, G. L. (2012) Dietary polyphenols in cancer prevention: the example of the flavonoid quercetin in leukemia, Ann. N. Y. Acad. Sci. 1259, 95-103.
[81] Mulholland, P., Ferry, D., Anderson, D., Hussain, S., Young, A., Cook, J., Hodgkin, E., Seymour, L., and Kerr, D. (2001) Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin, Ann. Oncol. 12, 245-248.
[82] Russo, M., Spagnuolo, C., Tedesco, I., Bilotto, S., and Russo, G. L. (2012) The flavonoid quercetin in disease prevention and therapy: facts and fancies, Biochem. Pharmacol. 83, 6-15.
[83] Murota, K., Matsuda, N., Kashino, Y., Fujikura, Y., Nakamura, T., Kato, Y., Shimizu, R., Okuyama, S., Tanaka, H., and Koda, T. (2010) α-Oligoglucosylation of a sugar moiety enhances the bioavailability of quercetin glucosides in humans, Arch. Biochem. Biophys. 501, 91-97.
[84] Makris, D. P., and Rossiter, J. T. (2002) An investigation on structural aspects influencing product formation in enzymic and chemical oxidation of quercetin and related flavonols, Food Chem. 77, 177-185.
[85] Kim, M. K., Park, K.-S., Lee, C., Park, H. R., Choo, H., and Chong, Y. (2010) Enhanced stability and intracellular accumulation of quercetin by protection of the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl (POM) promoiety, J. Med. Chem. 53, 8597-8607.
[86] Fremont, L. (2000) Biological effects of resveratrol, Life Sci. 66, 663-673.
[87] Richard, T., Pawlus, A. D., Iglésias, M. L., Pedrot, E., Waffo‐Teguo, P., Mérillon, J. M., and Monti, J. P. (2011) Neuroprotective properties of resveratrol and derivatives, Ann. N. Y. Acad. Sci. 1215, 103-108.
[88] Regev-Shoshani, G., Shoseyov, O., Bilkis, I., and Kerem, Z. (2003) Glycosylation of resveratrol protects it from enzymic oxidation, Biochem. J 374, 157-163.
[89] Nandi, S., Letham, D., Palni, L., Wong, O., and Summons, R. (1989) 6-Benzylaminopurine and its glycosides as naturally occurring cytokinins, Plant Sci. 61, 189-196.
[90] Doležal, K., Popa, I., Kryštof, V., Spíchal, L., Fojtíková, M., Holub, J., Lenobel, R., Schmülling, T., and Strnad, M. (2006) Preparation and biological activity of 6-benzylaminopurine derivatives in plants and human cancer cells, Biorg. Med. Chem. 14, 875-884.
[91] Frebort, I., Kowalska, M., Hluska, T., Frebortova, J., and Galuszka, P. (2011) Evolution of cytokinin biosynthesis and degradation, J. Exp. Bot. 62, 2431-2452.
[92] Ku, E. C., Lee, W., Kothari, H. V., and Scholer, D. W. (1986) Effect of diclofenac sodium on the arachidonic acid cascade, The American journal of medicine 80, 18-23.
[93] Swart, H., Breytenbach, J. C., Hadgraft, J., and du Plessis, J. (2005) Synthesis and transdermal penetration of NSAID glycoside esters, Int. J. Pharm. 301, 71-79.
[94] Linder, A. E., Poli, A., and de Lima e Silva, A. K. (2013) The effect of drugs that alter serotonin homeostasis in rat erectile function, The FASEB Journal 27, lb604.
[95] Stachulski, A. V., and Meng, X. (2013) Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides, Nat. Prod. Rep. 30, 806-848.
[96] Jove, R., Nam, S., and Skaltsounis, A.-L. (2013) Indirubin derivatives and uses thereof in treating chronic myelogenous leukemia. US20130210834 A1.
[97] Chen, Z.-Q., Liu, Y., Zhao, J.-H., Wang, L., and Feng, N.-P. (2012) Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system, International journal of nanomedicine 7, 1115.
[98] Silva, I. D., Gaspar, J., Da Costa, G. G., Rodrigues, A., Laires, A., and Rueff, J. (2000) Chemical features of flavonols affecting their genotoxicity. Potential implications in their use as therapeutical agents, Chem.-Biol. Interact. 124, 29-51.
[99] M Calderon-Montano, J., Burgos-Moron, E., Pérez-Guerrero, C., and López-Lázaro, M. (2011) A review on the dietary flavonoid kaempferol, Mini Rev. Med. Chem. 11, 298-344.
[100] Soromou, L. W., Chen, N., Jiang, L., Huo, M., Wei, M., Chu, X., Millimouno, F. M., Feng, H., Sidime, Y., and Deng, X. (2012) Astragalin attenuates lipopolysaccharide-induced inflammatory responses by down-regulating NF-κB signaling pathway, Biochem. Biophys. Res. Commun. 419, 256-261.
[101] Ni, Z., Zhang, Q., Qian, J., and Wang, L. (1999) Effect of Astragalin on matrix secretion and beta 1 integrin mRNA expression in human mesangial cells, Chin. Med. J. 112, 1063-1067.
[102] Ong, K. C., and Khoo, H.-E. (1997) Biological effects of myricetin, General Pharmacology: The Vascular System 29, 121-126.
[103] Sawruk, S. (1995) Method for treatment of osteoporosis. US5478579 A.
[104] Hiermann, A., Schramm, H., and Laufer, S. (1998) Anti-inflammatory activity of myricetin-3-O-β-D-glucuronide and related compounds, Inflamm. Res. 47, 421-427.
[105] Kleczkowski, L. A., Kunz, S., and Wilczynska, M. (2010) Mechanisms of UDP-glucose synthesis in plants, Crit. Rev. Plant Sci. 29, 191-203.
[106] Terasaka, K., Mizutani, Y., Nagatsu, A., and Mizukami, H. (2012) In situ UDP-glucose regeneration unravels diverse functions of plant secondary product glycosyltransferases, FEBS Lett. 586, 4344-4350.
[107] Son, M. H., Kim, B.-G., Kim, D. H., Jin, M., Kim, K., and Ahn, J.-H. (2009) Production of flavonoid O-glucoside using sucrose synthase and flavonoid O-glucosyltransferase fusion protein, J. Microbiol. Biotechnol. 19, 709-712.
[108] Zheng, Y., Anderson, S., Zhang, Y., and Garavito, R. M. (2011) The structure of sucrose synthase-1 from Arabidopsis thaliana and its functional implications, J. Biol. Chem. 286, 36108-36118.
[109] Römer, U., Schrader, H., Günther, N., Nettelstroth, N., Frommer, W. B., and Elling, L. (2004) Expression, purification and characterization of recombinant sucrose synthase 1 from Solanum tuberosum L. for carbohydrate engineering, J. Biotechnol. 107, 135-149.
[110] Barratt, D. P., Barber, L., Kruger, N. J., Smith, A. M., Wang, T. L., and Martin, C. (2001) Multiple, distinct isoforms of sucrose synthase in pea, Plant Physiol. 127, 655-664.
[111] Curatti, L., Porchia, A. C., Herrera-Estrella, L., and Salerno, G. L. (2000) A prokaryotic sucrose synthase gene (susA) isolated from a filamentous nitrogen-fixing cyanobacterium encodes a protein similar to those of plants, Planta 211, 729-735.
[112] Lee, C. M., Lu, C., Lu, W. M., and Chen, P.-C. (1995) Removal of nitrogenous compounds from wastewaters using immobilized cyanobacteria Anabaena CH3, Environ. Technol. 16, 701-713.
[113] Chen, P.-C., Fan, S.-H., Chiang, C.-L., and Lee, C.-M. (2008) Effect of growth conditions on the hydrogen production with cyanobacterium Anabaena sp. strain CH3, Int. J. Hydrogen Energy 33, 1460-1464.
[114] Wu, R., Diez, M. D. A., Figueroa, C. M., Machtey, M., Iglesias, A. A., Ballicora, M. A., and Liu, D. (2015) The crystal structure of Nitrosomonas europaea sucrose synthase reveals critical conformational changes and insights into the sucrose metabolism in prokaryotes, J. Bacteriol., JB. 00110-00115.
[115] 陳雅惠. (2013) 枯草桿菌醣基轉移酶 BcGT-1 中 Phe240, Phe132 及 Phe138 胺基酸殘基對類黃酮醣基化之影響, pp 1-82, 交通大學應用化學系學位論文.
[116] Hsieh, Y. C., Chiu, H. H., Huang, Y. C., Fun, H. K., Lu, C. Y., Li, Y. K., and Chen, C. J. (2014) Purification, crystallization and preliminary X-ray crystallographic analysis of glycosyltransferase-1 from Bacillus cereus, Acta Crystallogr F Struct Biol Commun 70, 1228-1231.
[117] Trott, O., and Olson, A. J. (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem. 31, 455-461.
[118] 許嘉郡. (2013) 豌豆蔗糖合成酶的表現, 性質研究和應用, pp 1-87, 交通大學應用化學系學位論文.
[119] 范家瑛. (2007) 幾丁質結合蛋白的應用, 交通大學理學院應用科技學程學位論文.
[120] 傅于烈. (2011) 枯草桿菌 UDP-glycosyltransferase 之受質專一性及應用研究, pp 1-92, 交通大學應用化學系學位論文.
[121] Bate, N., Butler, A. R., Smith, I. P., and Cundliffe, E. (2000) The mycarose-biosynthetic genes of Streptomyces fradiae, producer of tylosin, Microbiology 146 ( Pt 1), 139-146.
[122] Kiessling, L. L., and Splain, R. A. (2010) Chemical approaches to glycobiology, Annu. Rev. Biochem. 79, 619-653.
[123] Yoon, S. H., Fulton, D. B., and Robyt, J. F. (2010) Enzymatic synthesis of L-DOPA alpha-glycosides by reaction with sucrose catalyzed by four different glucansucrases from four strains of Leuconostoc mesenteroides, Carbohydr. Res. 345, 1730-1735.
[124] Schroeder, C., Lutterbach, R., and Stöckigt, J. (1996) Preparative biosynthesis of natural glucosides and fluorogenic substrates for β-glucosidases followed by in vivo 13C NMR with high density plant cell cultures, Tetrahedron 52, 925-934.
[125] Zhou, M., Hamza, A., Zhan, C. G., and Thorson, J. S. (2013) Assessing the regioselectivity of OleD-catalyzed glycosylation with a diverse set of acceptors, J. Nat. Prod. 76, 279-286.
[126] Commodari, F., Sclavos, G., Ibrahimi, S., Khiat, A., and Boulanger, Y. (2005) Comparison of 17β‐estradiol structures from X‐ray diffraction and solution NMR, Magn. Reson. Chem. 43, 444-450.
[127] Talisman, I. J., Kumar, V., Deschamps, J. R., Frisch, M., and Malhotra, S. V. (2011) Application of silver N-heterocyclic carbene complexes in O-glycosidation reactions, Carbohydr. Res. 346, 2337-2341.
[128] Ogiso, M., Fujimoto, Y., Ikekawa, N., and Ohnishi, E. (1986) Glucosidation of estradiol-17β in the cultured ovaries of the silkworm,Bombyx mori, Gen. Comp. Endocrinol. 61, 393-401.
[129] Xu, S., Yan, X., Zhang, Q., Xia, P., and Chen, Y. (2007) Unexpected rearrangement in the reaction of 7‐mercapto‐4‐methylcoumarin with 1‐mono‐and 1, 1‐dimethyl propargyl alcohols, Synth. Commun. 37, 3801-3808.
[130] Dasgupta, F., and Garegg, P. J. (1989) Synthesis of ethyl and phenyl 1-thio-1,2-trans-D-glycopyranosides from the corresponding per-O-acetylated glycopyranoses having a 1,2-trans-configuration using anhydrous ferric-chloride as a promoter, Acta Chem. Scand. 43, 471-475.
[131] Ikeda, Y., Furukawa, K., and Yamada, H. (2002) Simultaneous regioselective protection of phenyl 1-thioglucosides at the C-3 and C-6 or at the C-2 and C-6 hydroxy groups, Carbohydr. Res. 337, 1499-1501.
[132] Tanaka, T., Matsumoto, T., Noguchi, M., Kobayashi, A., and Shoda, S. (2009) Direct transformation of unprotected sugars to aryl 1-thio-β-glycosides in aqueous media using 2-chloro-1, 3-dimethylimidazolinium chloride, Chem. Lett. 38, 458-459.
[133] Katayama, H., Asahina, Y., and Hojo, H. (2011) Chemical synthesis of the S‐linked glycopeptide, sublancin, J. Pept. Sci. 17, 818-821.
[134] Thibodeaux, C. J., Melancon, C. E., and Liu, H. W. (2007) Unusual sugar biosynthesis and natural product glycodiversification, Nature 446, 1008-1016.
[135] Cowley, D., Duke, C., Liepa, A., MacLeod, J., and Letham, D. (1978) The structure and synthesis of cytokinin metabolites. 1. The 7-and 9-β-D-glucofuranosides and pyranosides of zeatin and 6-benzylaminopurine, Aust. J. Chem. 31, 1095-1111.
[136] Letham, D., Wilson, M., Parker, C., Jenkins, I., MacLeod, J., and Summons, R. (1975) Regulators of cell division in plant tissues: XXIII. The identity of an unusual metabolite of 6-benzylaminopurine, Biochimica et Biophysica Acta (BBA)-General Subjects 399, 61-70.
[137] Okkels, F. T., Ward, J. L., and Joersbo, M. (1997) Synthesis of cytokinin glucuronides for the selection of transgenic plant cells, Phytochemistry 46, 801-804.
[138] Du, W., and Hu, Y. (2004) Synthesis of fully protected N‐arylglycosylamines and factors affecting the configuration of C1‐substituents of N‐arylglycosylamines, Synth. Commun. 34, 2987-2992.
[139] Wirth, D. D., Baertschi, S. W., Johnson, R. A., Maple, S. R., Miller, M. S., Hallenbeck, D. K., and Gregg, S. M. (1998) Maillard reaction of lactose and fluoxetine hydrochloride, a secondary amine, J. Pharm. Sci. 87, 31-39.
[140] Pamplona, R., Bellmunt, M. J., Portero, M., Riba, D., and Prat, J. (1995) Chromatographic evidence for Amadori product formation in rat liver aminophospholipids, Life Sci. 57, 873-879.
[141] Aumiller, J. J., Mabashi-Asazuma, H., Hillar, A., Shi, X., and Jarvis, D. L. (2011) A new glycoengineered insect cell line with an inducibly-mammalianized protein N-glycosylation pathway, Glycobiology. 22, 417-428.
[142] Valliere-Douglass, J. F., Eakin, C. M., Wallace, A., Ketchem, R. R., Wang, W., Treuheit, M. J., and Balland, A. (2010) Glutamine-linked and non-consensus asparagine-linked oligosaccharides present in human recombinant antibodies define novel protein glycosylation motifs, J. Biol. Chem. 285, 16012-16022.
[143] Lomino, J. V., Naegeli, A., Orwenyo, J., Amin, M. N., Aebi, M., and Wang, L.-X. (2013) A two-step enzymatic glycosylation of polypeptides with complex N-glycans, Bioorganic & Medicinal Chemistry. 21, 2262-2270.
[144] Li, T., Du, Y., Cui, Q., Zhang, J., Zhu, W., Hong, K., and Li, W. (2013) Cloning, characterization and heterologous expression of the indolocarbazole biosynthetic gene cluster from marine-derived Streptomyces sanyensis FMA, Mar. Drugs 11, 466-488.
[145] Zhao, P., Bai, L., Ma, J., Zeng, Y., Li, L., Zhang, Y., Lu, C., Dai, H., Wu, Z., and Li, Y. (2008) Amide N-glycosylation by Asm25, an N-glycosyltransferase of ansamitocins, Chem. Biol. 15, 863-874.
[146] Sakakibara, H. (2006) Cytokinins: activity, biosynthesis, and translocation, Annu. Rev. Plant Biol. 57, 431-449.
[147] Breton, C., Šnajdrová, L., Jeanneau, C., Koča, J., and Imberty, A. (2006) Structures and mechanisms of glycosyltransferases, Glycobiology 16, 29R-37R.
[148] Bolam, D. N., Roberts, S., Proctor, M. R., Turkenburg, J. P., Dodson, E. J., Martinez-Fleites, C., Yang, M., Davis, B. G., Davies, G. J., and Gilbert, H. J. (2007) The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity, Proceedings of the National Academy of Sciences 104, 5336-5341.
[149] Bouktaib, M., Atmani, A., and Rolando, C. (2002) Regio- and stereoselective synthesis of the major metabolite of quercetin, quercetin-3-O-β-D-glucuronide, Tetrahedron Lett. 43, 6263-6266.
[150] 呂佳諭. (2011) 枯草桿菌 UDP-glycosyltransferase 之重要胺基酸殘基分析及其應用, pp 1-55, 交通大學應用化學系學位論文.
[151] Kwon, D.-J., and Bae, Y.-S. (2013) Flavonols from the stem bark of Acer komarovii, Chem. Nat. Compd. 49, 131-132.
[152] Ibraheim, Z. Z., and Salem, H. A. (2002) Phytochemical and pharmacological studies on Pulicaria orientalis jaub & sp, Bulletin of pharmaceutical sciences-assiut university 25, 189-200.
[153] Lemańska, K., Szymusiak, H., Tyrakowska, B., Zieliński, R., Soffers, A. E. M. F., and Rietjens, I. M. C. M. (2001) The influence of pH on antioxidant properties and the mechanism of antioxidant action of hydroxyflavones, Free Radic. Biol. Med. 31, 869-881.
[154] Razavi, S. M., Zahri, S., Zarrini, G., Nazemiyeh, H., and Mohammadi, S. (2009) Biological activity of quercetin-3-O-glucoside, a known plant flavonoid, uss. J. Bioorg. Chem. 35, 376-378.
[155] Süntar, I. P., Akkol, E. K., Yalçın, F. N., Koca, U., Keleş, H., and Yesilada, E. (2010) Wound healing potential of Sambucus ebulus L. leaves and isolation of an active component, quercetin 3-O-glucoside, J. Ethnopharmacol. 129, 106-114.
[156] Cermak, R., Landgraf, S., and Wolffram, S. (2004) Quercetin glucosides inhibit glucose uptake into brush-border-membrane vesicles of porcine jejunum, Br. J. Nutr. 91, 849-855.
[157] Kim, M.-S., and Kim, S.-H. (2011) Inhibitory effect of astragalin on expression of lipopolysaccharide-induced inflammatory mediators through NF-κB in macrophages, Arch. Pharmacal Res. 34, 2101-2107.
[158] Choi, J., Kang, H. J., Kim, S. Z., Kwon, T. O., Jeong, S.-I., and Jang, S. I. (2013) Antioxidant effect of astragalin isolated from the leaves of Morus alba L. against free radical-induced oxidative hemolysis of human red blood cells, Arch. Pharmacal Res. 36, 912-917.
[159] Kwon, H.-J., and Park, Y.-D. (2012) Determination of astragalin and astragaloside content in Radix Astragali using high-performance liquid chromatography coupled with pulsed amperometric detection, J. Chromatogr. 1232, 212-217.
[160] Malla, S., Pandey, R. P., Kim, B. G., and Sohng, J. K. (2013) Regiospecific modifications of naringenin for astragalin production in Escherichia coli, Biotechnol. Bioeng. 110, 2525-2535.
[161] Lee, Y. J., and Wu, T. D. (2001) Total synthesis of kaempferol and methylated kaempferol derivatives, J. Chin. Chem. Soc. 48, 201-206.
[162] Ye, G., and Huang, C. (2006) Flavonoids of Limonium aureum, Chem. Nat. Compd. 42, 232-234.
[163] Vale, H. F., M Mendes, M., S Fernandes, R., R Costa, T., IS Hage-Melim, L., A Sousa, M., Hamaguchi, A., I Homsi-Brandeburgo, M., C Franca, S., and HTP Silva, C. (2011) Protective effect of schizolobium parahyba flavonoids against snake venoms and isolated toxins, Curr. Top. Med. Chem. 11, 2566-2577.
[164] Iyer, V., and Subrahmanyam, V. (1985) Effect of structure on surfactance of sodium-salts of n-acylamino acids in aqueous-solutions, J. Indian Chem. Soc. 62, 507-512.
[165] Delmer, D. P., and Amor, Y. (1995) Cellulose biosynthesis, The Plant Cell 7, 987.
[166] Römling, U., and Galperin, M. Y. (2015) Bacterial cellulose biosynthesis: diversity of operons, subunits, products, and functions, Trends Microbiol. 23, 545-557.
[167] Macheda, M. L., Rogers, S., and Best, J. D. (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer, J. Cell. Physiol. 202, 654-662.
[168] Brown, R. S., and Wahl, R. L. (1993) Overexpression of glut‐1 glucose transporter in human breast cancer an immunohistochemical study, Cancer 72, 2979-2985.
[169] Kurata, T., Oguri, T., Isobe, T., Ishioka, S. i., and Yamakido, M. (1999) Differential expression of facilitative glucose transporter (GLUT) genes in primary lung cancers and their liver metastases, Jap. J. Cancer Res. 90, 1238-1243.
[170] Calvaresi, E. C., and Hergenrother, P. J. (2013) Glucose conjugation for the specific targeting and treatment of cancer, Chemical Science 4, 2319-2333.
[171] Norris, A. J., Whitelegge, J. P., Faull, K. F., and Toyokuni, T. (2001) Analysis of enzyme kinetics using electrospray ionization mass spectrometry and multiple reaction monitoring: fucosyltransferase V, Biochemistry 40, 3774-3779.