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  • 學位論文

針對蛋白質酪胺酸磷脂質水解酶次族群發展高專一性活性標示之研究

Development of activity-based probes with high specificity for protein tyrosine phosphatase subfamilies

指導教授 : 羅禮強
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摘要


蛋白質酪胺酸磷脂質水解酶在訊號傳遞的機理上扮演一個相當重要的角色,因此解析蛋白質酪胺酸磷脂質水解酶次族群的活性與分佈,對生物醫學的研究上將會有前瞻性的貢獻。本論文中,我們合成出仿酪胺酸磷酸酯的捕捉機制單元,並以Fmoc方法來進行組合式的固相合成,藉由改變七胜肽其中兩個位置氨基酸的種類,來建構出線性與環形的活性標示分子庫。這兩大類活性標示分子庫將用於比較它們對於蛋白質酪胺酸磷脂質水解酶標示效能的差異,以及用於篩選出針對蛋白質酪胺酸磷脂質水解酶次族群具高專一性的活性探針。

並列摘要


Protein tyrosine phosphatases (PTPs) play an important role in regulatory signal transduction. It’s a prospective contribution to realize the activities and distribution of PTP subfamilies for the studies of biomedicine. Herein we synthesize phosphotyrosine mimic device which applies for combinatorial solid phase synthesis with Fmoc strategy. Via change two positions of the designed sequence with seven different amino acids to build up the activity-based probe library of the linear and cyclic peptides. Finally we compare to the different labeling efficiency of two type comformations of this library and screen these probes with high specificity for PTP subfamilies.

參考文獻


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