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Substrate interaction inhibits γ-secretase production of amyloid-ß peptides.
Zhao, Jing; Xiao, Yuanyuan; Liu, Xinyue; Kim, Soohyun; Wu, Xianzhong; Barros, Marilia; Zhuang, Ran; Hou, Xuben; Zhang, Yingkai; Robakis, Nikolaos K; Li, Yue-Ming; Dordick, Jonathan S; Ubarretxena-Belandia, Iban; Wang, Chunyu.
Afiliación
  • Zhao J; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.
  • Xiao Y; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.
  • Liu X; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.
  • Kim S; 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.
  • Wu X; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Barros M; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Zhuang R; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.
  • Hou X; Department of Medicinal Chemistry and Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
  • Zhang Y; Department of Chemistry, New York University, New York, NY 10003, USA.
  • Robakis NK; 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.
  • Li YM; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Dordick JS; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu and Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA and Department of Chemical and Biological Engineering, Rensselaer Polytechnic Ins
  • Ubarretxena-Belandia I; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA and Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, E-48940, Leioa, Spain and Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Spain.
  • Wang C; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu and Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA and Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institut
Chem Commun (Camb) ; 56(17): 2578-2581, 2020 Feb 27.
Article en En | MEDLINE | ID: mdl-32016207
ABSTRACT
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-ß with µM IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Secretasas de la Proteína Precursora del Amiloide Límite: Humans Idioma: En Revista: Chem Commun (Camb) Asunto de la revista: QUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Secretasas de la Proteína Precursora del Amiloide Límite: Humans Idioma: En Revista: Chem Commun (Camb) Asunto de la revista: QUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos