Saccharomyces cerevisiae as a platform for assessing sphingolipid lipid kinase inhibitors

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dc.contributor.authorKharel, Yugeshen
dc.contributor.authorAgah, Sayehen
dc.contributor.authorHuang, Taoen
dc.contributor.authorMendelson, Anna J.en
dc.contributor.authorEletu, Oluwafunmilayo T.en
dc.contributor.authorBarkey-Bircannl, Peteren
dc.contributor.authorGesualdil, Jamesen
dc.contributor.authorSmith, Jeffrey S.en
dc.contributor.authorSantos, Webster L.en
dc.contributor.authorLynch, Kevin R.en
dc.contributor.departmentChemistryen
dc.contributor.departmentCenter for Drug Discoveryen
dc.date.accessioned2019-06-04T16:57:39Zen
dc.date.available2019-06-04T16:57:39Zen
dc.date.issued2018-04-19en
dc.description.abstractSuccessful medicinal chemistry campaigns to discover and optimize sphingosine kinase inhibitors require a robust assay for screening chemical libraries and for determining rank order potencies. Existing assays for these enzymes are laborious, expensive and/or low throughput. The toxicity of excessive levels of phosphorylated sphingoid bases for the budding yeast, Saccharomyces cerevisiae, affords an assay wherein inhibitors added to the culture media rescue growth in a dose-dependent fashion. Herein, we describe our adaptation of a simple, inexpensive, and high throughput assay for assessing inhibitors of sphingosine kinase types 1 and 2 as well as ceramide kinase and for testing enzymatic activity of sphingosine kinase type 2 mutants. The assay was validated using recombinant enzymes and generally agrees with the rank order of potencies of existing inhibitors.en
dc.description.notesThis work was supported by NIH/NIGMS R01 GM104366 & NIH/NIGMS R01 GM121075 to KRL & WLS, NIH R01 GM075240 to JSS, NIGMS: https://www.nigms.nih.gov/Pages/default.aspx; University of Virginia Summer Research Internship Program fellowships to JG and PBB https://med.virginia.edu/diversity/programs/srip/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.sponsorshipNIH/NIGMS [R01 GM104366, R01 GM121075]; NIH [R01 GM075240]; NIGMS; University of Virginia Summer Research Internship Program fellowshipsen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0192179en
dc.identifier.eissn1932-6203en
dc.identifier.issue4en
dc.identifier.othere0192179en
dc.identifier.pmid29672528en
dc.identifier.urihttp://hdl.handle.net/10919/89743en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleSaccharomyces cerevisiae as a platform for assessing sphingolipid lipid kinase inhibitorsen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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