本文利用固相胜?合成法，合成多種以XPRK、HPRK單元為模型的胜?序列，研究XPRK、HPRK單元胜?對DNA的結合作用，合成之胜?分為三大類：一、環狀胜?類、二、含NMP（N-methylpyrrole）結構之直鏈胜?類、三、直鏈胜?類。利用我們所合成的胜?初步以凝膠電泳實驗測試胜?與DNA結合的能力，而改變XPRK單元中X殘基對DNA的結合能力有不同以及修飾內部胺基酸，並將Pro改為Hyp希望提高結合力。環狀胜?對DNA有良好結合能力，環狀十四?比環狀九?有較佳的結合能力，其中以CYR-14表現較好。含NMP之直鏈胜?，發現十?對DNA的結合能力優於九?，而九?的又優於直鏈沒加NMP之直鏈胜?，如PyHy-9優於PyHy-6，而含NMP之胜?又以KQHy-10能力最好。只含胺基酸的直鏈胜?以Hyp-12的結合能力最好。未來期望針對XPRK、HPRK單元胜?進一步深入研究，篩選出對DNA具有專一性結合的胜?，以DNA足跡法（DNA footprinting）研究胜?對DNA的序列結合專一性（DNA sequence-specific recognition），使之成為新DNA結合劑並運用於基因治療以及基因調控的製劑。 This thesis describes solid-phase synthesis and DNA binding assay of peptides containing the XPRK motif. Three categories of peptides are being investigated: 1. Cyclic peptides,2. Linear peptides containing 4-amino-1-methylpyrrole- 2-carboxylic acid (NMP) residues, 3. Linear peptides。 Various peptides containing XPRK motifs and hydroxyproline (Hyp) residues displayed good DNA binding ability, as shown in agarose gel electrophoresis assay. 14-mer cyclic peptides displayed better DNA binding property than 9-mer cyclic peptides. 10-mer linear peptides containing NMP residues are better than 9-mer peptides and 9-mer peptides with NMP residues are better than peptides without NMP residues. This work provides fundamental research in new peptides with potential DNA sequence-specific recognition which is useful in future gene therapy and gene modulation research. DNA footprinting studies will provide quantitative parameters of sequence-specific binding sites.
