蛋白質之間的交互作用(PPIs)在細胞的生理功能上扮演一個重要的角色，它們的失調往往成為各種疾病的誘因。因此，針對蛋白質交互作用設計藥物做為治療疾病的策略，吸引了很多科學家的目光。介白素-6(IL-6)/醣蛋白130(GP130)/STAT3生物途徑的啟動對於類風濕性關節炎、前列腺癌、乳癌等癌症的發展相當重要。
在本論文中，我們設計了一個流程用來建立虛擬化合物庫，這些化合物是針對IL-6與受體GP130交互作用的介面使用基於片段的藥物設計(FBDD)重新創造的，用來阻斷這些交互作用，進而治療與此生物途徑相關的疾病。由於透過基於片段的藥物設計創造出來的化合物常常被認為是難以實際合成的，開發相應的化學合成途徑需要大量的成本，儘管合成出來也不能保證其是否具有生物活性，因此我們在各大化合物資料庫中尋找結構與我們創造的虛擬化合物相似、被記錄有生物活性的化合物做為間接的驗證或是藥物的重新定位。這些虛擬化合物的可合成性分數(SA score)也會被標註上去做為參考。未來如果生物測定的結果證實這些結構相似的藥物確實有生物活性，我們創造的這些虛擬化合物可以開始進行後續的修飾，其可合成性分數可以做為是否要進行實際合成的參考。

Protein-protein interactions (PPIs) play an important role in physiological function of living cells. Their dysregulation can cause numerous diseases. Therefore, modulating PPIs had attracted considerable attention for designing drugs for some years.
The triggering of IL-6/GP130/STAT3 pathway, which results in multiple oncogene transcriptions, is critical for progression of multiple types of cancers such like prostate cancer and breast cancer. In this thesis, we reported a workflow to build a library of de novo virtual compounds, which are designed from beginning on the IL-6 /GP130 interface, using fragment-based approach. Since virtual compounds designed from fragment-based approach are usually considered hard to synthesize, similarity search of virtual hit on compound databases is performed for indirect validation and drug repositioning. Synthetic accessibility score (SA score) of each compound is calculated for annotation. If further bioassays performed with drugs identified by drug repositioning show any active result, these virtual compound will be optimized and SA score of each will be taken as reference of synthesis.

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