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研究生:莊博鈞
研究生(外文):PoChun Chuang
論文名稱:可與DNA結合多之合成
論文名稱(外文):Synthesis of some DNA binding peptides
指導教授:佘亮佘亮引用關係
指導教授(外文):Sheh, Leung
學位類別:碩士
校院名稱:東海大學
系所名稱:化學系
學門:自然科學學門
學類:化學學類
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
中文關鍵詞:專一性結合切割胺基酸
外文關鍵詞:Sequence specific bindingcleavageamino acid
相關次數:
  • 被引用被引用:1
  • 點閱點閱:87
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  • 下載下載:2
  • 收藏至我的研究室書目清單書目收藏:0
本論文主要以固相胜合成法,合成對DNA有高親和能力的胜作為藥物載體,發展對附著DNA有順序專一性的結合物或切割劑。
一.合成Ser-Pro-X-X系列來自調節基因蛋白質的衍生物,為一穩定
β-turn結構,有利於纏繞並以離子鍵結合DNA。例如:
Ser-Pro-Lys-His-Ser-Pro-Lys-His-Ser-Pro-Lys-His-Ser-Pro-Lys-His-CONH2 (16-KH4)
二.合成Asn-Arg-Arg系列來自腫瘤細胞壞死因子片段中第30-35段的衍生物,藉由這些段作為藥物的載體。例如:
Asn-Arg-Arg-Ala-Asn-Trp-CONH2 (6W-NRR)
6 5 4 3 2 1
三.合成以短胜為主,並將此胜作為氮苯芥丁酸(Chlorambucil, CRB)藥物的載體,在離胺酸(Lysine)的ε或α位置側鏈上,與CRB偶合,以獲得更佳之DNA專一性結合及切割。例如:
CRB-Lys-Arg-Asn-Pro-Arg-Lys-CONH2 (6-α-C-KR)
6 5 4 3 2 1
以上多以凝膠電泳偵測其對DNA的切割能力及對DNA的凝膠滯留效應。亦將與其他研究室合作進行DNA足跡法(Footprinting),更進一步確定結合在DNA的位置及其鹼基。
This thesis reports synthesis of peptides with high affinity to DNA and DNA cleavage agent with potential sequence specificity.
1.Synthesis of Ser-Pro-X-X series , which is based on the sequence of histones and has β-turn conformation to wind around DNA with ionic interactions. For example:
Ser-Pro-Lys-His-Ser-Pro-Lys-His-Ser-Pro-Lys-His-Ser-Pro-Lys-His-CONH2 (16-KH4)
2.Synthesis of Asn-Arg-Arg series of peptides is based on the amino acid sequence corresponding to fragment 30-35 of TNF-α. For example:
Asn-Arg-Arg-Ala-Asn-Trp-CONH2 (6W-NRR)
6 5 4 3 2 1
3.Synthesis of chlorambucil-peptide conjugates, which may produce DNA cleavage with sequence specificity. For example:
CRB-Lys-Arg-Asn-Pro-Arg-Lys-CONH2 (6-α-C-KR)
6 5 4 3 2 1
By means of agarose electrophoresis, all of the peptides were examined for DNA binding , cleavage as well as gel retardation effects . DNA footprinting studies will be carried out in collaboration with other laboratories.
目錄……………………………………………………1
中文摘要………………………………………………2
英文摘要………………………………………………4
圖表目錄………………………………………………6
縮寫目…………………………………………………11
壹、緒論………………………………………………14
貳、實驗部分
一、藥品與儀器…………………………………..27
二、原理與方法…………………………………..32
三、實驗步驟……………………………………..42
參、結果與討論………………………………………125
肆、結論………………………………………………156
伍、參考資料………………………………………..157
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