title: Identification of selective covalent inhibitors of platelet activating factor acetylhydrolase 1B2 from the screening of an oxadiazolone-capped peptoid-azapeptoid hybrid library.
abstract: A potent and selective inhibitor of platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) is described. The compound was derived by improvement of a modest affinity primary hit isolated from the screening of a bead-displayed peptoid-azapeptoid hybrid library tethered to an oxadiazolone 'warhead'. The oxadiazolone moiety of the inhibitors was found to react covalently with the active site serine residue of PAFAH1B2. This screening strategy may be useful for the identification of many selective, covalent inhibitors of serine hydrolases.
authors.affiliation: Department of Chemistry, School of Natural Sciences, Shiv Nadar University, Dadri, Uttar Pradesh-201314, India.
authors.forename: Bani Kanta
authors.initials: BK
authors.lastname: Sarma
authors.affiliation: Departments of Chemistry, Scripps Research Institute, Scripps Florida, 130 Scripps Way, #3A2, Jupiter, Fl 33458, USA.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Departments of Chemistry, Scripps Research Institute, Scripps Florida, 130 Scripps Way, #3A2, Jupiter, Fl 33458, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D008956:Models, Chemical; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry*; D019151:Peptide Library; D034444:Peptoids / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001372:Aza Compounds; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D019151:Peptide Library; D034444:Peptoids; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
keywords: Combinatorial chemistry; High throughput screening; PAFAH1B2; Peptoid; Serine hydrolase