臺灣博碩士論文加值系統

果膠廣泛存在於水果和蔬菜中，普遍應用於食品、醫藥、化妝品等行業，已經使用多年。本研究以果膠的單體半乳糖醛酸，與立體異構物的葡萄糖醛酸做為材料，進行化學修飾反應。將半乳糖醛酸和葡萄糖醛酸一號碳和六號碳上羧基均接上甲氧基，之後分個別在鹼性溶液中室溫條件下，以及在DMF溶液高溫下，把六號碳上甲氧基，置換成羥肟胺酸，再進行一連串抗氧化活性的測試，包括DPPH自由基清除、保護DNA免受氫氧自由基攻擊、氫氧自由基清除、超氧自由基清除、抗脂質過氧化、抑制過氧亞硝酸氧化，實驗結果顯示半乳糖醛酸和葡萄糖醛酸均無效果，但是兩者的羥肟胺酸衍生物GluA-NHOH 與 GalA-NHOH皆具有明顯抗氧化效果。
兩個起始反應物與其羥肟胺酸衍生物進行抑制一氧化氮生成測定，以LPS誘導細胞株RAW264.7所產生的NO，發現只有半乳糖醛酸衍生物GalA-NHOH具有抑制NO的效果，而在以MTT進行細胞毒性測試，發現GalA-NHOH在測試濃度下，對細胞的毒性相當低。
另一方面，兩起始物和兩羥肟胺酸衍生物進行抑制 semicarbazide-sensitive amine oxidase (SSAO)和雙胺氧化酶測定中，發現不論酵素來源是小牛血漿或是豬血漿，在SSAO抑制曲線測定和SSAO活性染色，均很清楚顯示兩衍生物具抑制效果，而兩起始反應物半乳糖醛酸和葡萄糖醛酸均無效果，而對於抑制雙胺氧化酶曲線測定，兩羥肟胺酸衍生物的抑制能力也優於兩起始物。探討SSAO與兩羥肟胺酸衍生物的酵素動力學抑制型態，以Lineweaver-Burk分析結果發現，兩條線也是交會於X軸，表示GluA-NHOH 與 GalA-NHOH與基質(benzylamine)對於小牛血漿內SSAO進行非競爭型抑制，GluA-NHOH 與 GalA-NHOH的抑制常數(Ki) 個別為0.039mM 和0.027 mM。

The pectin is generally found in fruits and vegetables and has been widely used in food industry, medical, and cosmetics. The galacturonic acid (GalA) is the monomer of pectins, and the glucuronic acid (GluA) is its isomer. In the first, GalA was reacted with equal volumes of acidic methanol solution at 4 ℃ for five days, and GluA was also reacted with equal volumes of methanol solution at 90℃ for 12 hours. The methoxyl group was added at the C-1 and C-6 of them. Then, they were reacted with alkaline hydroxylamine at room temperature and N, N-Dimethylformamide at 80℃ respectively to repare GalA and GluA hydroxamic acid derivatives (GalA-NHOH and GluA-NHOH). They were used to test the antioxidant and antiradical activities in comparison with the GalA and GluA.
The scavenging activities of GluA-NHOH and GalA-NHOH for DPPH radicals were very apparent as compared with GluA and GalA. Similarly, using electron spin resonance (ESR) for scavenging hydroxyl radicals, it was also found that the hydroxamic acid derivatives can present quite obvious effects of antiradical activities. Futhermore, GluA-NHOH and GalA-NHOH not only exhibited protection from hydroxyl radical-mediated DNA damage and scavenging superoxide radicals induced by xanthine oxidase. but also showed anti-lipid peroxidation and anti-peroxynitrite through dihydrorhodamine 123.
On the other hand, it was found that only GalA-NHOH is proven to inhibit the LPS-induced NO production, and Gal-NHOH is exhibited low cytotoxicity under the measurement condition by MTT assay.

While, in the semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity from bovine or pig plasma, both GluA-NHOH and GalA-NHOH can inhibit SSAO effectively, but neither GluA nor GlaA. It was also found that GluA-NHOH and GalA-NHOH could inhibit diamine oxidase (DAO) from porcine kidney as dose-dependent patterns. By using SSAO activity staining on 7.5% polyacrylamide gels, it was comfirmed the inhibitory activities of GluA-NHOH and GalA-NHOH against SSAO. While GluA-NHOH (0.04 mM) or GalA-NHOH (0.03 mM) were added, GluA-NHOH and GalA-NHOH showed noncompetitive inhibition compared to benzylamine. The apperant inhibition constant (Ki) of GluA-NHOH and GalA-NHOH were 0.039 mM and 0.027 mM, respectively.

目 錄
頁次
目錄……………………………………………………………… I

圖目錄……………………………………………………………… IV
縮寫表……………………………………………………………… VII
中文摘要…………………………………………………………… VIII
英文摘要………………………………………………………… X


壹、文獻回顧
（一）半乳糖醛酸(Galacturonic acid)…………………………… 1
（二）果膠(Pectin)……………………………………………….. 2
（三）羥肟胺酸(Hydroxamic acid)……………………………… 6
（四）自由基與抗氧化概說………………………….………… 9
（五）胺氧化酶(Amine oxidase)……………………………….. 19
（六）研究動機………………………………………………….. 25

貳、材料與方法
一、材料、藥品與儀器……………………………………………. 26
二、實驗方法……………………………………………………… 28
（一）葡萄糖醛酸羥污胺酸衍生物的製備….………………… 28
（二）半乳糖醛酸羥污胺酸衍生物的製備.....................……… 30
（三）DPPH自由基的清除測定……………………..…............ 32
（四）保護DNA免受氫氧自由基攻擊之能力測定...………… 32
（五）電子自磁共振儀測定氫氧自由基之清除測定…..……… 33
（六）超氧自由基清除測定…………………………………….. 34
（七）抑制黃嘌呤氧化酶………………………..……………… 35
（八）脂質過氧化測定.……………………………………….… 36
（九）抑制peroxynitrite氧化DHR 測定………………..……. 37
（十）抑制一氧化氮生成測定………………………..………… 37
（十一）SSAO 抑制活性測定………………………....……….. 40
（十二）雙胺氧化酶抑制曲線測定…………………………...… 41
（十三）SSAO 活性染色……………………............................. 41
（十四）酵素動力學探討……………………………………….. 45

參、結果與討論
（一）1-methoxyl-glucuronohydroxamic acid (GluA-NHOH)結構判定……………………………………………….....
46
（二）1-methoxyl-galacuronohydroxamic acid (GalA-NHOH)結構判定……………………………………………….....
49
（三）DPPH自由基的清除測定………………………...……… 52
（四）保護DNA免受氫氧自由基攻擊之能力測定…………… 55
（五）電子自磁共振儀測定氫氧自由基之清除測定…..……… 59
（六）超氧自由基清除測定…………………………….……… 67
（七）抑制黃嘌呤氧化酶(xanthine oxidase)活性測定………… 71
（八）脂質過氧化測定……………………………….…………. 74
（九）抑制過氧亞硝酸氧化DHR 123測定……………………. 78
（十）抑制一氧化氮生成測定…………………………….…… 81
（十一）細胞毒性測試……………………………….………… 88
（十二）抑制SSAO活性測定……………….………………… 91
（十三）抑制雙胺氧化酶活性測定………………..…………… 97
（十四）SSAO 活性染色……………………………………..… 100
（十五）酵素動力學之抑制型態探討………………………..… 105

肆、結論……………………………………………………………… 112

伍、未來與展望……………………………………………….……… 114

陸、參考文獻……………………………………………………….... 115

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