(I)以固相胜肽合成法合成組胺酸胜肽並修飾聚乙二胺樹枝狀分子作為銅離子螯合劑 (II) 合成以胜肽修飾之藥物作為抗攝護腺癌藥劑

(I) Synthesis Histidine Peptide by SPPS and Modified PAMAM Dendrimers as Copper Ion Binders (II) Synthesis of Peptides-Modified Compounds as Specific Anti-Prostate Cancer Agent

吳欣蓓(Hsin-Pei Wu)

指導教授 ： 高佳麟

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2009年)

摘要

樹枝狀分子由於其具有表面眾多官能基的特色，而組胺酸對某些金屬離子有很好的螯合能力，如：銅離子和鎳離子。在本實驗中，欲在樹枝狀分子外眾多的官能基上，以由不同數量組胺酸所組成的胜肽做修飾。其中，以固相胜肽合成 (SPPS) 合成所需的胜肽。在將胜肽N端之保護基之後，於合成過程中所遇到的問題 (如：溶解度、純化等等) ，大部份皆能成功地克服。同時，亦成功地將組胺酸及所合成出的胜肽修飾於聚乙二胺樹枝狀分子表面，並且透過電化學的方式得知此類產物，的確具有螯合銅離子及定量水溶液中銅離子的能力。在未來，這類產物可能會具有成為金屬螯合劑的潛力。

目前，有鑑於攝護腺癌仍是至今前十大癌症之一。而藥物修飾特定的胜肽已是常見的方式，除了能增加藥物的水溶性之外，亦能有效地到達治療的目的地以減低藥物的副作用。針對攝護腺癌，我們選擇了BBN (Bombesin) 做為所欲合成的胜肽，其序列為QWAVGHLM。起初，我們以固相胜肽合成的方式直接合成最終產物，但藥物於TFA中被破壞，以致於無法成功地取得所合成之產物。因此，我們必需先合成並純化所需之胜肽，而後再將胜肽修飾於藥物上。最後，再以UV測定的方式比較胜肽修飾前後藥物之溶解度。

關鍵字

聚乙二胺樹枝狀分子 ； 胜肽銅離子 ； 攝護腺癌

並列摘要

There are many surface groups on the dendrimers surfaces. Histidine accesses the good binding affinity of metal ions, such as copper and nickel ions. In this thesis, we modified the surface groups of PAMAM dendrimer with different number of histidine peptide. The designed peptides were prepared by solid phase peptide synthesis (SPPS). Meanwhile, we modified the PAMAM dendrimer with histidine residue successfully, and the ability to bind copper was confirmed through the electrochemistry. In the future, these compounds may be a good metal binder.

Meanwhile, prostate cancer is one of the top ten cancer incidence. The most important way to improve the drugs solubility and diminish side effect is to modify the drugs with specific peptides. For the prostate cancer, we choose the Bombesin (BBN) as our target peptides, the sequences are QWAVGHLM. At first, we synthesized the final compounds on solid phase, but the drug was decomposed in TFA which is necessary to collect peptide from resin. Thereafter, we have to synthesize and purify the peptide first then to modify the drug with the peptide. With this, we compared the solubility before and after the peptide modification by UV detection.

並列關鍵字

PAMAM dnedrimer ； peptide ； copper ion ； prostate cancer

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