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研究生:謝忠益
研究生(外文):Chung-Yee Shieh
論文名稱:N-acetyl-leucyl-leucyl-norleucinal衍生物合成之研究
論文名稱(外文):The study and synthesis of N-acetyl-leucyl-leucyl-norleucinal derivatives
指導教授:蘇聖芳蘇聖芳引用關係陳清玉陳清玉引用關係
指導教授(外文):Shen-Fang SuChing-Yuh Chern
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:82
中文關鍵詞:液態peptide合成法ALLN衍生物P-糖蛋白
外文關鍵詞:solution-phase peptide synthesisP-glycopriteinALLN derivatives
相關次數:
  • 被引用被引用:3
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  • 下載下載:15
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中文摘要
P-glycoprotein (Pgp)是一個與抗癌藥物之多重抗藥性(multiple-drug resistance)有關的運送子。Pgp其主要作用能將藥物自細胞內排出,因而降低藥物於細胞內的蓄積。
文獻指出厭水性的peptide,如ALLN (N-acetyl-leucyl-leucyl- norleucinal)、ALLM (N-acetyl-leucyl-leucyl-methiminal)、leupeptin (N-acetyl-leucyl-leucyl-arginal)為 Pgp的受質或抑制劑。本實驗以N-acetyl- leucyl-leucine為主架構,欲合成出一系列的線性peptide,有助於未來將此系列peptide應用於與Pgp間 interaction 的研究。
本實驗選用液態peptide合成法,合成出N-acetyl- leucyl-leucine benzyl、N-acetyl- leucyl-leucine、N-acetyl- leucyl-leucyl-tryptophanol、N-acetyl- leucyl-leucyl-CBZ-lysinol、 N-acetyl- leucyl-leucyl- phenylalaninol。
英文摘要
P-glycoprotein (Pgp), the multidrug resistance gene (mdr1) product, reduces the intracellular accumulation of a variety of drugs by pumping drugs out of membranes.
Studies have demonstrated that hydrophobic tripeptides N-acetyl- leucyl- leucyl-norleucinal (ALLN), N-acetyl- leucyl-leucyl-methiminal (ALLM) and N-acetyl-leucyl-leucyl-arginal (leupeptin) are Pgp substrates/inhibitors. We would like to synthesize a series of tripeptides (N-acetyl-leu-leu-X ) and to study the interaction between the tripeptides and Pgp.
We employ liquid-phase peptide synthesis method to obtain. We synthesize the N-acetyl-leucyl-leucine benzyl、N-acetyl-leucyl-leucine、N-acetyl-leucyl-leucyl-tryptophanol、N-acetyl-leucyl-leucyl-CBZ-lysinol、 N-acetyl-leucyl-leucyl-phenylalaninol.
目錄
中文摘要 I
英文摘要 II
誌謝 III
目錄 IV
表目錄 V
圖目錄 VI
縮寫 VIII
第壹章 緒論 1
第貳章 peptide之合成 3
第一節、peptide合成之發展 3
第二節、peptide合成法之介紹 6
第三節、peptide的純化 24
第參章 peptide合成的應用 26
第肆章 研究目的 37
第伍章 實驗材料、儀器及方法 38
第一節、材料 38
第二節、儀器 40
第三節、實驗方法 42
第陸章 結果 53
第柒章 討論 73
參考文獻 77

表目錄
表1、一般peptide合成時所用的側鏈保護基 15
表2、常用於移除peptide的混合試劑 22
表3、本實驗合成所得之peptide 73

圖目錄
圖1、 Stepwise的peptide合成 ..9
圖2、 Merrifield的solid-phase peptide synthesis .20
圖3、 oxytocin之結構式 .26
圖4、 R121和R205的結構式 32
圖5、 Retro-synthesis 之1 42
圖6、 Retro-synthesis 之2 43
圖7、 Tryptophanol(1)1H核磁共振光譜圖 58
圖8、 Tryptophanol(1)13C核磁共振光譜圖 59
圖9、 Tryptophanol(1)Mass 60
圖10、Benzyloxycarbonly lysinol (2)1H核磁共振光譜圖 61
圖11、Benzyloxycarbonly lysinol (2)13C核磁共振光譜圖 62
圖12、Benzyloxycarbonly lysinol (2)Mass 63
圖13、N-acetyl-leucyl-leucyl benzyl (3)1H核磁共振光譜圖 64
圖14、N-acetyl-leucyl-leucyl benzyl (3)13C核磁共振光譜圖 65
圖15、N-acetyl-leucyl-leucyl benzyl (3)Mass 66
圖16、N-acetyl-leucyl-leucine (4)1H核磁共振光譜圖 67
圖17、N-acetyl-leucyl-leucine (4)13C核磁共振光譜圖 68
圖18、N-acetyl-leucyl-leucine (4)Mass 69
圖19、N-acteyl-leucyl-leucyl-phenylalaninol (5)1H核磁共振光譜圖 70
圖20、N-acteyl-leucyl-leucyl-phenylalaninol (5)13C核磁共振光譜圖 71
圖21、N-acteyl-leucyl-leucyl-phenylalaninol (5)Mass 72
圖22、ALLN (N-acteyl-leucyl-leucyl-norleucinal) 之結構式 75
圖23、未純化之tripeptide結構式 75
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