Dataset Information

Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library.

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.

SUBMITTER: Kung PP

PROVIDER: S-EPMC7294708 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library.

Kung Pei-Pei PP Bingham Patrick P Burke Benjamin J BJ Chen Qiuxia Q Cheng Xuemin X Deng Ya-Li YL Dou Dengfeng D Feng Junli J Gallego Gary M GM Gehring Michael R MR Grant Stephan K SK Greasley Samantha S Harris Anthony R AR Maegley Karen A KA Meier Jordan J Meng Xiaoyun X Montano Jose L JL Morgan Barry A BA Naughton Brigitte S BS Palde Prakash B PB Paul Thomas A TA Richardson Paul P Sakata Sylvie S Shaginian Alex A Sonnenburg William K WK Subramanyam Chakrapani C Timofeevski Sergei S Wan Jinqiao J Yan Wen W Stewart Albert E AE

ACS medicinal chemistry letters 20200410 6

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 ...[more]

PMID: 32550998

Dataset Information

Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library.

Publications

Characterization of Specific <i>N</i>-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library.

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