合成親水性樹枝狀胜肽以增進氫氧基磷酸鈣分散能力

氫氧基磷酸鈣在生物醫學的應用廣泛，例如作為硬組織替代的支架，或是活性成分吸附之載體，近年也大量使用在整形美容的填充材料，但其容易聚集的特性使其不易在水溶液中均質分散。我們利用親水性胜肽與氫氧基磷酸鈣結合，增加氫氧基磷酸鈣之懸浮性，透過固相胜肽合成策略成功地獲得目標化合物，包含兩條直鏈狀胜肽，Asp6-mPEG2000和Gly3Asp3-mPEG2000(產率: 25.8 %-42.9 %)及樹枝狀(G:2)-dendri-PAMAM-(Asp6)6;(NH2)9;(mPEG2000)1，(G:2)-dendri-PAMAM-(T-(Asp6)2)8;(NH2)6;(mPEG2000)2 (產率: 14.6%-30%)。Asp6 的側鏈羧基是與氫氧基磷酸鈣螯合的主要位置，且PEG 也可以提高整體與水的作用。我們發現，樹枝狀胜肽與HAp螯合，其結合率為直鏈狀胜肽的1.3倍。當奈米尺度的氫氧基磷酸鈣與直鏈狀胜肽結合後，沉降量到達45% T時，所花時間為1450秒，而樹枝狀胜肽所花時間為3600秒，比直鏈狀胜肽的時間長2150秒。因此，我們成功地改善氫氧基磷酸鈣在水溶液中的分散能力，以期許提高氫氧基磷酸鈣未來的應用潛力。

關鍵字

氫氧基磷酸鈣；樹枝狀胜肽

並列摘要

Hydroxyapatite ( HAp ) has been used in biomedical materials, such as hard tissue replacement bracket or be the carrier for active ingredients absorption. In the recent year, it also widely used as fill material in plastic surgery. However, it has high challenge to disperse HAp particles in aqueous solution. The HAp beads easyily clump together and result in lumpiness in the treated area. We used hydrophilic peptides combined modification, to increase the suspension of HAp in aqueous solution. Through solid phase peptide synthesis approach, two linear peptides, Asp6-PEG2000 and Gly3Asp3-PEG2000 ( yield: 25.8%-42.9%), and two dendritic peptides (G:2)-dendri-PAMAM-(Asp6)6;(NH2)9;(mPEG2000)1, (G:2)-dendri-PAMAM-(T-(Asp6)2)8;(NH2)6;(mPEG2000)2 ( yield: 14.6%-30%) were prepared. The carboxyl side chain of Asp6 offers the key residue to bind with HAp and the PEG provides the interaction with water. The binding ratio of dendritic peptide with HAp was dramatically increase and is 1.3 fold than what linear one does. Furthermore, it takes 1450 seconds to precipitate the linear peptide combined with nanosize HAp, but the dendritic one takes 3600 seconds when it combined with nanosize HAp. It is 2150 seconds longer than the linear peptides work. Therefore, we have successfully improved the suspension ability of HAp in aqueous solution, and wish to enhance the potential of HAp for future applications.