Peptide-Based 2-Aminophenylamide Probes for Targeting Endogenous Class?I Histone Deacetylase Complexes.

ABSTRACT: Lysine deacetylases or histone deacetylases (HDACs) remove acetylation markers from numerous cellular proteins, thereby regulating their function and activity. Recently established peptide probes containing the HDAC-trapping amino acid ?-aminosuberic acid ?-hydroxamate (AsuHd) have been used to investigate the compositions of HDAC complexes in a site-specific manner. Here we report the new HDAC-trapping amino acid 2-amino-8-[(2-aminophenyl)amino]-8-oxooctanoic acid (AsuApa) and the utility of AsuApa-containing probes for HDAC complex profiling on a proteome-wide scale. Unlike AsuHd-containing probes, AsuApa enriched only HDACs 1, 2, and 3 efficiently and was the most potent probe tested for capturing the last of these. These findings indicate that the inherent specificity of reported small-molecule pimelic diphenylamide HDAC inhibitors is preserved in AsuApa and that this HDAC-trapping amino acid represents a potent tool for investigating class?I HDAC complexes.

SUBMITTER: Seidel J 

PROVIDER: S-EPMC6973067 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature