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Bioorg Med Chem. 2016 Sep 1;24(17):3953-3963. doi: 10.1016/j.bmc.2016.04.047. Epub 2016 Apr 23.

Identification of selective covalent inhibitors of platelet activating factor acetylhydrolase 1B2 from the screening of an oxadiazolone-capped peptoid-azapeptoid hybrid library.

Author information

1
Department of Chemistry, School of Natural Sciences, Shiv Nadar University, Dadri, Uttar Pradesh-201314, India.
2
Departments of Chemistry, Scripps Research Institute, Scripps Florida, 130 Scripps Way, #3A2, Jupiter, Fl 33458, USA.
#
Contributed equally

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.

KEYWORDS:

Combinatorial chemistry; High throughput screening; PAFAH1B2; Peptoid; Serine hydrolase

PMID:
27160052
PMCID:
PMC4972644
DOI:
10.1016/j.bmc.2016.04.047
[Indexed for MEDLINE]
Free PMC Article

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