Perfluorinated hydroxamic acids are potent and selective inhibitors of HDAC-like enzymes from Pseudomonas aeruginosa. Issue 7 (1st April 2017)

• Record Type: Journal Article
• Authors: Meyners, Christian; Wolff, Benjamin; Kleinschek, Alexander; Krämer, Andreas; Meyer-Almes, Franz-Josef
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 7(2017)
• Page Start: 1508
• Page End: 1512
• Publication Date: 2017-04-01
• Subjects: HDAC inhibitors -- Pseudomonas aeruginosa -- Perfluorinated hydroxamic acids -- Selectivity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.02.050
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.