膠原蛋白是哺乳動物中含量最多的蛋白質，已廣泛應用於生醫材料上。為增加其在生醫材料上的應用性，許多研究在尋找有效的製備方法，來促使短鏈的膠原蛋白模擬胜肽自組裝成高階結構。在本研究的第一部分中，我們將組胺酸(His)引入膠原蛋白模擬胜肽，藉由組胺酸與金屬的配位作用促進膠原蛋白模擬胜肽自組裝成高階超分子結構。我們使用(POG)9為基底胜肽，藉著在不同位置置入His探討修飾在胜肽兩端組胺酸的有無，以及中間置換的個數對於整體自組裝速率和結構的影響。實驗結果顯示，胜肽兩端的組胺酸之導入有助於加速自組裝，而且中間的組胺酸可以幫助側向生長形成較立體的結構。相較之下，只有中間做組胺酸置換的胜肽，在自組裝上需要長時間的延遲期，因此會有較單一方向的聚集而形成較緊密有序的薄片結構。雖然，我們對於膠原蛋白的自組裝過程尚不完全清楚，但在我們的研究中可以發現胜肽上組胺酸置換的位置及數目，對於自組裝速度及結構上均有明顯的影響，希望這樣的結果可以對未來膠原蛋白自組裝設計有更多的了解及幫助。

在第二部分的實驗，我們引入了鋅金屬酶具有水解催化活性的概念，設計出類似於碳酸酐酶的催化配位結構，利用三股螺旋胜肽兩端的組胺酸可以提供較集中的配位基來與金屬作用，進而作為催化酯類水解的活性位置。實驗結果發現在中性環境下所得到的催化效率普遍不佳，而是要在大於可以使組胺酸側鏈去質子化的pH環境下，才可以觀察到顯著的催化效果。而在高pH值9.75且沒有金屬添加的情況下，HG(POG)4(PHG)(POG)4GH胜肽鏈具有卓越的催化效率，較以往研究中所報導的三股捲曲螺旋 (coiled-coil) 高出三倍，此結果有助於未來以膠原蛋白三股螺旋作為基底的酯類水解催化劑之發展。

Collagen is the most abundant protein in mammals and has been widely used in biomedical materials. Searching for an effective way to assemble short collagen mimetic peptides (CMPs) into a high order structure has received many attentions and been an emerging research topic for increasing biomaterial applicability. In the first part of this thesis, we have incorporated histidine (His) into CMPs to promote their self-assembly into supramolecular structures via His-metal coordination. In this study, we used (POG)9 as the parent peptide to design a series of CMPs with His residues incorporated into different positions. Our aim was to investigate the effects of the number and location of His residues on the self-assembly of CMPs. The results showed that incorporting His residues into the ends of a CMP could speed the self-assembly process but the assemblies were less ordered. In contrast, the CMPs without His residues at their ends could assemble into a more ordered and microflorettes like structures though the assembly process was very slow. Although we were not able to clarify the self-assembly process of collagen, we did find the impact of the location of His replacement on the rate of self-assembly and the morphology of assemblies. Our results may be useful and helpful for the future development of collagen-related materials.

In the second part of the experiment, we mimicked the active site of zinc metalloenzymes to design metal-CMPs assemblies as catalysts for ester hydrolysis. We used the His residues at both ends of the triple helix as the ligands to coordinate with metal ions and serve as the catalytic active site for ester hydrolysis. It is analogous to the active site of the zinc metalloenzyme carbonic anhydrase (CA). Our results indicated that the catalytic efficiency of the designed peptides was not good at neutral pH, but increased significantly at higher pH values, reflecting the deprotonation of a His side chain. In addition, at pH 9.75 and without the addition of metal, HG(POG)4(PHG)(POG)4GH peptide exhibited an excellent catalytic efficiency, which is three times greater than the previous reported three strained coiled-coils. And these results may be helpful for the development of catalysts for the ester hydrolysis with the collagen triple helix as the based peptide.

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