白樺酸（Betulinic acid）是一種萃取自白樺樹的三萜類化合物，具有抗病毒、抗瘧疾、抗腫瘤、抗發炎的活性。白樺酸具有治療當前醫藥界急欲克服的病症之潛力，然而白樺酸的細胞標的物質仍未知。為了要找尋白樺酸的細胞標的物質，本論文中將白樺酸固定在基質，製備成固定相白樺酸親和性管柱，並且研究此管柱的效用。經由前人的研究可知白樺酸可以抑制牛胰臟磷脂質分解酵素（bp-PLA2）的活性，在本論文證明固定相白樺酸可以與磷脂質分解酵素作交互作用。此交互作用可以改變磷脂質分解酵素的生物功能：經由酵素活性和細胞毒性的試驗顯示白樺酸可以抑制磷脂質分解酵素之活性並且可以抑制蛇毒磷脂質分解酵素的細胞毒性。白樺酸與磷脂質分解酵素的交互作用可望應用在磷脂質分解酵素的純化與毒性中和。本論文證明固定相白樺酸確實會與牛胰臟或蛇毒中之磷脂質分解酵素有交互作用，除此之外，固定相白樺酸管柱也可以與蛇毒中心臟毒，cardiotoxin gamma有交互作用，而cardiotoxin gamma的蛋白質三度空間結構與磷脂質分解酵素無相似之處，這表示在細胞中有機會找到非磷脂質分解酵素的白樺酸標的物質。本論文的貢獻即是設計此固定相白樺酸親和性管柱並測試其效用以應用來找尋白樺酸的細胞標的物質。

Betulinic acid (BA), a triterpenoid of white birch (Betula alba), exhibits anti-viral, anti-malarial, anti-tumor and anti-inflammatory activities. It has been shown to be an inhibitor of bovine pancreatic PLA2 (bp-PLA2); however, its cellular targets remain to be explored. As an effort of identifying the cellular target of BA, the BA immobilized matrix was made and the utility of the immobilized column was studied. Enzymatic activity assay and cytotoxicity test were used to confirm that the physical interaction between BA and PLA2 could change the PLA2 biological function. This interaction may be mediated by electrostatic interaction and hydrophobic interaction dependent on Ca2+. Eventually, the results identified a physical interaction of BA and bp-PLA2 or N-PLA2. It was suggested that this interaction could be applied to PLA2 purification and N-PLA2 toxin neutralization. In this thesis, the BA-immobilized column exhibited an affinity with bp-PLA2 or N-PLA2. Surprisingly, the column also binds cardiotoxin γ, which does not resemble to PLA2 in tertiary structure. The results represent the possibility of the cellular targets of BA besides PLA2. It was proved that BA-immobilized affinity column designed in this thesis might be applied to explore cellular targets of BA.

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