| Literature DB >> 32550998 |
Pei-Pei Kung1, Patrick Bingham1, Benjamin J Burke1, Qiuxia Chen2, Xuemin Cheng2, Ya-Li Deng1, Dengfeng Dou2, Junli Feng1, Gary M Gallego1, Michael R Gehring1, Stephan K Grant1, Samantha Greasley1, Anthony R Harris1, Karen A Maegley1, Jordan Meier3, Xiaoyun Meng2, Jose L Montano3, Barry A Morgan4,2, Brigitte S Naughton1, Prakash B Palde1, Thomas A Paul1, Paul Richardson1, Sylvie Sakata1, Alex Shaginian2, William K Sonnenburg2, Chakrapani Subramanyam1, Sergei Timofeevski1, Jinqiao Wan2, Wen Yan1, Albert E Stewart1.
Abstract
Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.Entities:
Year: 2020 PMID： 32550998 PMCID： PMC7294708 DOI： 10.1021/acsmedchemlett.0c00029
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345