Substrate interaction inhibits γ-secretase production of amyloid-β peptides

Jing Zhao; Yuanyuan Xiao; Xinyue Liu; Soohyun Kim; Xianzhong Wu; Marilia Barros; Ran Zhuang; Xuben Hou; Yingkai Zhang; Nikolaos K. Robakis; Yue Ming Li; Jonathan S. Dordick; Iban Ubarretxena-Belandia; Chunyu Wang

doi:10.1039/c9cc09170j

Substrate interaction inhibits γ-secretase production of amyloid-β peptides

Jing Zhao
, Yuanyuan Xiao
, Xinyue Liu
, Soohyun Kim
, Xianzhong Wu
, Marilia Barros
, Ran Zhuang
, Xuben Hou
, Yingkai Zhang
, Nikolaos K. Robakis
, Yue Ming Li
, Jonathan S. Dordick
, Iban Ubarretxena-Belandia
, Chunyu Wang

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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-β with μM IC₅₀. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.

Original language	English
Pages (from-to)	2578-2581
Number of pages	4
Journal	Chemical Communications
Volume	56
Issue number	17
DOIs	https://doi.org/10.1039/c9cc09170j
State	Published - 28 Feb 2020

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title = "Substrate interaction inhibits γ-secretase production of amyloid-β peptides",

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-β with μM IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.",

author = "Jing Zhao and Yuanyuan Xiao and Xinyue Liu and Soohyun Kim and Xianzhong Wu and Marilia Barros and Ran Zhuang and Xuben Hou and Yingkai Zhang and Robakis, \{Nikolaos K.\} and Li, \{Yue Ming\} and Dordick, \{Jonathan S.\} and Iban Ubarretxena-Belandia and Chunyu Wang",

note = "Publisher Copyright: This journal is {\textcopyright} The Royal Society of Chemistry.",

year = "2020",

month = feb,

day = "28",

doi = "10.1039/c9cc09170j",

language = "English",

volume = "56",

pages = "2578--2581",

journal = "Chemical Communications",

issn = "1359-7345",

publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - Substrate interaction inhibits γ-secretase production of amyloid-β peptides

AU - Zhao, Jing

AU - Xiao, Yuanyuan

AU - Liu, Xinyue

AU - Kim, Soohyun

AU - Wu, Xianzhong

AU - Barros, Marilia

AU - Zhuang, Ran

AU - Hou, Xuben

AU - Zhang, Yingkai

AU - Robakis, Nikolaos K.

AU - Li, Yue Ming

AU - Dordick, Jonathan S.

AU - Ubarretxena-Belandia, Iban

AU - Wang, Chunyu

PY - 2020/2/28

Y1 - 2020/2/28

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85080957982

U2 - 10.1039/c9cc09170j

DO - 10.1039/c9cc09170j

M3 - Article

C2 - 32016207

AN - SCOPUS:85080957982

SN - 1359-7345

VL - 56

SP - 2578

EP - 2581

JO - Chemical Communications

JF - Chemical Communications

IS - 17

ER -

Substrate interaction inhibits γ-secretase production of amyloid-β peptides

Abstract

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