title: Perfluorinated hydroxamic acids are potent and selective inhibitors of HDAC-like enzymes from Pseudomonas aeruginosa.
abstract: A series of perfluorinated SAHA (PFSAHA) was prepared and profiled against a panel of human and bacterial members of the Histone deacetylase (HDAC) family. Some of the active substances show nanomolar inhibitory activity and several hundred fold selectivity for the HDAC like enzyme PA3774 from P. aeruginosa. The extraordinary selectivity against human HDACs results from the distinct oligomeric state of PA3774 which consists of two head-to-head dimers. The binding pocket is defined by the surface of both opposite monomers confining the access of ligands to the active site. In addition, the aromatic cap group of PFSAHA undergoes an edge-to-face aromatic interaction with phenylalanine from the opposite monomer.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295 Darmstadt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Meyners
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295 Darmstadt, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolff
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295 Darmstadt, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kleinschek
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295 Darmstadt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Krämer
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295 Darmstadt, Germany. Electronic address: franz-josef.meyer-almes@h-da.de.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Meyer-Almes
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D001665:Binding Sites; D005466:Fluorocarbons / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D005466:Fluorocarbons; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D006655:Histone Deacetylases
keywords: HDAC inhibitors; Perfluorinated hydroxamic acids; Pseudomonas aeruginosa; Selectivity