針對磷酸酯水解酵素發展可調控辨識單元的活性標示

Development of Tunable Activity Probes for Protein Tyrosine Phosphatase

黃俞淵(Yu-Yuan Huang)

指導教授 ： 羅禮強

國立臺灣大學/理學院/化學研究所/碩士(2007年)

https://doi.org/10.6342/NTU.2007.10035

摘要

PTP在生理方面扮演著相當重要的角色，參予了細胞生長、分化、代謝以及訊息傳遞等工作，因此本研究針對PTP設計並合成出活性標示分子。
活性標示分子的設計主要是分成四大部分(1)辨識單元(2)捕捉機制(3)連接橋(4)發報端，利用辨識端和酵素的結合，當酵素和辨識端進行反應產生高活性的中間體，酵素立即和此中間體發生鍵結達到標示效果，再以發報端來進行訊號發報或進行純化，每個部分都各司其職。
本研究的設計，辨識端是一個修飾的Tyrosine phosphate，當活性標示分子被水解，進行1,4-elimination產生quinone methide中間體來捕捉PTP；另外利用胺基酸的變化作為可調控的辨識單元（R1,R2），探討不同胜肽鏈對酵素的專一性。

關鍵字

活性標示 ； 水解酵素

並列摘要

Protein tyrosine phosphatases (PTPs) played crucial role in physiology, participate in such work as cell growth, differentiation, and metabolism. Here we developed three activity probes for PTPs.
Hydrolysis of these activity probes by PTP appeared to be specific, rendering their selective labeling to PTP. When the P-OAr bond in our probes is cleaved by PTP. It quickly undergoes 1,4-elimination of the fluoride, hence resulting in the formation of the highly electrophilic quinone methide. The quinone methide could alkylate the nearby nucleophiles on the phosphatases.
A complete activity probe contains four structural units: (1) recognition head; (2) trapping device; (3) linker; (4) reporter group. We synthesized three regulable activity probes by tripeptide sequence.

並列關鍵字

PTP ； activity probe ； phosphatase

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