膠原蛋白 (Collagen) 是哺乳類動物體內含量最多的蛋白質，具有獨特右手螺旋結構，由三條序列為 (Xaa-Yaa-Gly)n 的左旋胜肽，藉由彼此間形成氫鍵，產生螺旋結構。在此研究中，我們試圖尋找一簡單而有效的方法來誘發和幫助膠原蛋白三股螺旋結構的形成。在二十個天然的胺基酸當中，組氨酸 (Histidine) 和金屬有好的配位能力，因此，我們設計並合成ㄧ系列在碳端 (C terminus) 和氮端 (N terminus) 含有組氨酸 (Histidine) 嵌入的模擬膠原蛋白胜肽，GHP(PPG)7、(PPG)7PHG、HG(PPG)7、HG(PPG)7GH 和 (PPG)7GH，希望藉由組氨酸 (Histidine) 和金屬離子之間所形成的配位作用力，幫助模擬胜肽形成穩定的三螺旋結構。
從圓二分光儀 (circular dichroism，CD) 和 NMR 測量中，顯示出在無金屬離子狀況下，這些胜肽除了 (PPG)7PHG 之外並無法形成三股螺旋結構，但當加入金屬離子後，其中兩模擬胜肽 (PPG)7GH 和HG(PPG)7GH可以形成較穩定的三螺旋結構，熔點 (melting temperature，Tm) 大約為 20 ℃，金屬離子和組氨酸 (Histidine) 之間的配位能力不同，使 (PPG)7GH 和HG(PPG)7GH 胜肽在形成三股螺旋結構的過程產生對金屬之選擇性，我們的結果顯示，銅離子 (Cu2+)、亞銅離子 (Cu+) 和鎳離子 (Ni2+)，可誘發此二模擬胜肽形成三股螺旋結構。而鐵離子 (Fe3+)、鈷離子 (Co2+) 和鋅離子 (Zn2+) 等離子則無法誘使三股螺旋結構的形成。
另外，動力學之量測顯示，銅離子 (Cu2+) 和亞銅離子 (Cu+) 所誘發三股螺旋結構之折疊之速率比鎳離子 (Ni2+) 來的快，且在同一金屬離子的條件下，(PPG)7GH 形成三股螺旋結構的速率比 HG(PPG)7GH 快。

Collagen is the most abundant protein in mammalian tissues with a unique right-handed triple helix structure which is composed of three left-handed PPⅡ peptide chains. Each peptide chain is rich in (Xaa-Yaa-Gly) sequence repeats，the triple helix is formed by hydrogen bonding between the chains. Among the nature amino acids, histidine is known for having high binding affinity with metal ions and is often found in the metal binding sites in protons. In this work, we try to find a simple way to induce the folding of a collagen triple helix. Thus, we have designed and synthesized a series of His-containing collagen mimics, including GHP(PPG)7, (PPG)7PHG, HG(PPG)7, HG(PPG)7GH and (PPG)7GH, for the metal binding study.
Circular dichroism (CD) and NMR measurements showed that (PPG)7PHG could form slightly stable triple helices in the present of metal ions, while HG(PPG)7GH and (PPG)7GH could be induced to fold into the triple helical comformation by metal ions. The increase in melting temperatures (Tm) can be up to about 20 ˚C, HG(PPG)7 fail to fold into a triple helix upon adding metal ions, indicating that the C-terminal metal-histidine coordination is the driving force to assist the folding. The results are also consistent with the folding mechanism of collagen that initiates at C-terminus and propagates to the N-terminus. There is metal selectivity for the peptide mimics to form triple helices, due to the difference in the binding affinity between metal ions and histidine. The metal dependent measurements have further shown that Cu2+、Cu+ and Ni2+ could induce the folding of HG(PPG)7GH and (PPG)7GH while Fe3+、Co2+ and Zn2+ could not. Besides, the kinetic measurement also showed that the folding rate of triple helices induced by Cu2+ and Cu+ were faster than by Ni2+. In the present of the same metal ion, (PPG)7GH formed triple helices faster than HG(PPG)7GH because the additional metal-histidine coordivation on the N-terminus might perturb the inter-strand alignment and impede the folding process. In conclusion, the His-containing collagen mimetic peptides can fold into a stable triple helix with the assistance of metal ions, and their metal selectivity could provide a potential application in biosensor.

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