title: Synthesis and evaluation of acyl protein thioesterase 1 (APT1) inhibitors.
abstract: Lipid-modified proteins play decisive roles in important biological processes such as signal transduction, organisation of the cytoskeleton and vesicular transport. Lipidation of these proteins is essential for correct biological function. Among the modifications with lipids, prenylation and myristoylation are well understood. However, the machinery of palmitoylation is still under investigation. Recently, an enzyme, acyl protein thioesterase 1 (APT1), that may play a regulatory role in the palmitoylation cycle of H-Ras and G-protein alpha subunits, was purified. Motivated by this work, several inhibitors of APT1 were designed, synthesized and biologically evaluated leading to highly active compounds.
authors.affiliation: University of Leipzig, Institute of Organic Chemistry, Johannisallee 29, 04103 Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Biel
authors.forename: Patrick
authors.initials: P
authors.lastname: Deck
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giannis
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; C402226:LYPLA1 protein, human; D013869:Thiolester Hydrolases