合成含仿磷酸酪胺酸基團之Diketopiperazine分子庫

Abstract

Diketopiperazines由於含有獨特的雜環體系，因而存在著各式各樣的生物活性，本論文中，目標是建構一個帶有仿磷酸酪胺酸基團之diketopiperazine組合式分子庫，而兩組線性型式雙胜肽(Fmoc-X-cpY-OMe and Fmoc-cpY-X-NH2)也同時合成出做為對照研究的目的，這裡X代表19個胺基酸殘基和11個側鏈有保護的氨基酸，而cpY代表仿磷酸酪胺酸殘基，因此，分子庫是由三個子集組合而成，包含31個diketopierazines、31個Fmoc-X-cpY-OMe以及28個Fmoc-cpY-X-NH2，共90個化合物個別製備完成，此分子庫對於各酵素家族做為抑制劑之篩選目前已在進行中，包括蛋白質酪胺酸磷酯質水解酶和激酶。

Diketopiperazines have a wide variety of biological activities due to their peculiar heterocyclic system. In this thesis, we aimed to construct a combinatorial library of diketopiperazines carrying a phosphotyrosine mimetic group. For the purpose of comparative study, two linear forms of dipeptides (Fmoc-X-cpY-OMe and Fmoc-cpY-X-NH2) were also synthesized. Here X stands for the 19 amino acid residues and for the 11 side chain-protected amino acids; whereas cpY stands for the phosphotyrosine mimetic residue. Therefore, the library is composed of three subsets. Totally, 90 compounds were individually prepared, including 31 diketopierazines, 31 Fmoc-X-cpY-OMe, and 28 Fmoc-cpY-X-NH2. This molecular library is currently being screened for inhibitors toward various enzyme families, including protein tyrosine phosphatases and kinases.