底物相互作用抑制 γ-分泌酶产生淀粉样β肽。
Substrate interaction inhibits γ-secretase production of amyloid-β peptides.
机构信息
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Center for Molecular Biology and Genetics of Neurodegeneration, Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
出版信息
Chem Commun (Camb). 2020 Feb 27;56(17):2578-2581. doi: 10.1039/c9cc09170j.
Combining NMR, mass spectrometry, AlphaLISA and cell assays, we discovered a compound C1 that binds C-terminal juxtamembrane lysines at the transmembrane domain of the amyloid precursor protein (APPTM) and inhibits γ-secretase production of amyloid-β with μM IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.
通过结合 NMR、质谱、AlphaLISA 和细胞检测，我们发现了一种名为 C1 的化合物，它可以结合淀粉样前体蛋白（APPTM）跨膜域的 C 端临近膜赖氨酸，以 μM 的 IC50 抑制 γ-分泌酶生成淀粉样-β。我们的工作表明，靶向 APPTM 是 AD 药物发现中的一种新颖且可行的策略。
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