我們成功的以X-ray結構為基礎去設計合成出日本血吸蟲麩銨基硫轉換酶的抑制劑，可以分別佔據榖胱甘肽活性位置（G site）、疏水性活性位置（H site）、和二聚體之間的活性位置（L site），化合物34-36比起未經修飾的榖胱甘肽三肽抑制劑（化合物4a、4b、11a、11b）抑制效果好將近（10-490倍），也讓我們在以後設計疏水性配體上提供了更好的方向。 另外我們也利用固相合成的方法嘗試改變各種不同的疏水性配體部分來尋求更好的先驅物，進而比較對日本血吸蟲麩銨基硫轉換酶的抑制效果。 We describe the discovery and synthesis of inhibitors of SjGST, by use of a structure-based drug design approach, capable of occupying the glutathione binding site（G site）, electrophile binding site（H site） and the dimmer interface （L site）of the SjGST. The trivalent inhibitors (34-36) achieved not only an excellent enhancement (10-490 folds) in the inhibitory potency compared to the monovalent analogues, but also an effective modification in selecting a hydrophobic moiety with flexible linker by the aid of molecular dynamics simulations. Besides, we try to use solid phase to modify different hydrophobic moiety in order to find the lead compound. Similarly, the inhibitory potency toward SjGST will be measured in due course.
