title: Probing the structure-activity relationship of endogenous histone deacetylase complexes with immobilized peptide-inhibitors.
abstract: Histone deacetylases (HDACs) are key regulators of numerous cellular proteins by removing acetylation marks from modified lysine residues. Peptide-based HDAC probes containing α-aminosuberic acid ω-hydroxamate have been established as useful tools for investigating substrate selectivity and composition of endogenous HDAC complexes in cellular lysates. Here we report a structure-activity study of potential HDAC-probes containing derivatives of the hydroxamate moieties. While most of these probes did not recruit significant amounts of endogenous HDACs from cellular lysates, peptides containing Nε-acetyl-Nε-hydroxy-L-lysine served as HDAC probe. The recruitment efficiency varied between HDACs and was generally lower than that of α-aminosuberic acid ω-hydroxamate probes, but showed a similar global interaction profile. These findings indicate that Nε-acetyl-Nε-hydroxy-L-lysine might be a useful tool for investigations on HDAC complexes and the development of HDAC inhibitors. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, D-72076, Tübingen, Germany.
authors.forename: Julia
authors.identifier: http://orcid.org/0000-0002-7265-8093
authors.initials: J
authors.lastname: Sindlinger
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, D-72076, Tübingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Bierlmeier
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, D-72076, Tübingen, Germany.
authors.forename: Lydia-Christina
authors.initials: LC
authors.lastname: Geiger
authors.affiliation: Plant Proteomics, Max Planck-Institute for Plant Breeding Research, Carl-von-Linné Weg 10, D-50829, Cologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kramer
authors.affiliation: Plant Proteomics, Max Planck-Institute for Plant Breeding Research, Carl-von-Linné Weg 10, D-50829, Cologne, Germany.|Institute for Plant Biology and Biotechnology, University of Muenster, Schlossplatz 7, 48149, Muenster, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Finkemeier
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, D-72076, Tübingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schwarzer
mesh_terms: D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010455:Peptides; D006655:Histone Deacetylases
keywords: HDAC inhibitors; HDACs; activity-based probes; lysine acetylation