Tunghai University Institutional Repository:Item 310901/4084
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    Please use this identifier to cite or link to this item: http://140.128.103.80:8080/handle/310901/4084


    Title: 新DNA切割劑之合成及切割研究之一
    Other Titles: Synthesis of novel DNA cleavage agents
    Authors: 周炳任
    Contributors: 佘亮
    Sheh, Leung
    東海大學化學系
    Keywords: 固相胜?;合成法;基因療法;胜?
    Solid phase peptide synthesis;gene therapy;peptide
    Date: 2002
    Issue Date: 2011-05-19T05:28:10Z (UTC)
    Abstract: 本研究利用固相胜?合成法(Solid phase peptide synthesis,SPPS)合成對DNA具有切割能力之多?,合成之多?分為兩大類: 一、純多?無偶聯任合試劑 例如: His-Pro-Arg-Lys-(Py)4-His-Pro-Arg-Lys-CONH2 (PyH-12) 二、多?-氮芥苯丁酸偶聯物(peptide-Chlorambucil conjugates) 例如:CLB-Asn-Arg-Arg-Ala-Asn-Ala-CONH2 (CLB-NR-6) 我們用固相胜?合成法合成多?,以凝膠電泳方法偵查多?或其與CLB偶聯物對DNA是否有凹槽結合(froove binding)或切割(cleaving)能力; 再以高解析電泳找出其作用位。另外,我們以分子模擬(molecular modeling)預測其立體結構從預測的立體結構來修正藥物的設計,使理論計算與實際實驗能相輔相成。此二類之多?因不須借助任何金屬離子、藥劑或能量即可切割DNA,為新型之DNA切割劑。藉以不斷改良此二類之多?,期望可用於將來的基因療法。
    This thesis reports the use of solid phase peptide synthesis technology for the preparation of two series of novel DNA cleavage agents. Series 1 : Peptides. For example : His-Pro-Arg-Lys-(Py)4-His-Pro-Arg-Lys-CONH2 (PyH-12) Series 2 : Peptide-Chlorambucil conjugates. For example : CLB-Asn-Arg-Arg-Ala-Asn-Ala-CONH2 (CLB-NR-6) The synthetic peptides were subjected to agarose electrophoresis to determine its ability to nick supercoiled DNA. The sequence specificity of DNA cleavage by these agents was further studied using high resolution polyacrylamide gel electrophoresis was then employed to study. We also use molecular modeling to examine the interaction of the drugs to the minor or major grooves of DNA. These drugs are developed as potential agents for future gene therapy.
    Appears in Collections:[Department of Chemistry ] Theses and Dissertations

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