Substrate interaction inhibits γ-secretase production of amyloid-β peptides Research Letter
| Authors: | Zhao, J.; Xiao, Y.; Liu, X.; Kim, S.; Wu, X.; Barros, M.; Zhuang, R.; Hou, X.; Zhang, Y.; Robakis, N. K.; Li, Y. M.; Dordick, J. S.; Ubarretxena-Belandia, I.; Wang, C. |
| 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. This journal is © The Royal Society of Chemistry. |
| Keywords: | controlled study; unclassified drug; human cell; drug targeting; mass spectrometry; protein analysis; enzyme inhibition; carboxy terminal sequence; protein interaction; drug structure; cell assay; drug research; nuclear magnetic resonance spectroscopy; enzyme specificity; drug protein binding; alzheimer disease; amyloid precursor protein; gamma secretase; amyloid beta protein[1-40]; amyloid beta protein[1-42]; human; article; ic50; concentration (parameter); compound c1; nootropic agent |
| Journal Title: | Chemical Communications |
| Volume: | 56 |
| Issue: | 17 |
| ISSN: | 1359-7345 |
| Publisher: | Royal Society of Chemistry |
| Date Published: | 2020-02-28 |
| Start Page: | 2578 |
| End Page: | 2581 |
| Language: | English |
| DOI: | 10.1039/c9cc09170j |
| PUBMED: | 32016207 |
| PROVIDER: | scopus |
| PMCID: | PMC8219260 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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