Functional analysis of g-secretase, which concerned with generation of amiroide-b-pepilde1

我们研究了一种有效的抑制剂的筛选和γ-分泌酶的功能分析，该酶被确定为阿尔茨海默病(AD)的重要治疗靶点。在我们基于高效抑制剂DAPT(1)的研究过程中，我们开发了一种利用聚合物结合试剂合成光亲和探针的方法。此外，通过探针的合成和光亲和标记实验表明，DAPT的主要直接靶分子是从家族性AD遗传学调查中发现的前苯胺1C末端片段(PS1CTF)。此外，通过与各类抑制剂的竞争光标记实验，我们剖析了DAPT的抑制机制。

We investigated the screening of a potent inhibitor and the functional analysis of y-secretase, which was identified as an important therapeutic target for Alzheimer's disease (AD). During the course of our investigation based on potent inhibitor DAPT (1), we developed a fitile synthetic method for a photoaffinity probe by utilizing the polymer-bound reagent. Furthermore, the utility of the reagent was demonstrated by synthesis of the probe and the photoaffinity labeling experiments of the probe clarified that the major direct target molecules for the DAPT are preseniline 1 C-terminal fragments (PS1 CTFs), which were discovered from the genetically investigation of familial AD. Additionally, a competing photolabeling experiment of the probe against various class of inhibitors, we dissected the inhibitory mechanism of DAPT.