Mining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leads

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dc.contributor.authorAng, Kenny K. H.en
dc.contributor.authorRatnam, Joselineen
dc.contributor.authorGut, Jirien
dc.contributor.authorLegac, Jenniferen
dc.contributor.authorHansell, Elizabethen
dc.contributor.authorMackey, Zachary B.en
dc.contributor.authorSkrzypczynska, Katarzyna M.en
dc.contributor.authorDebnath, Anjanen
dc.contributor.authorEngel, Juan C.en
dc.contributor.authorRosenthal, Philip J.en
dc.contributor.authorMcKerrow, James H.en
dc.contributor.authorArkin, Michelle R.en
dc.contributor.authorRenslo, Adam R.en
dc.contributor.departmentBiochemistryen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2018-06-01T19:04:48Zen
dc.date.available2018-06-01T19:04:48Zen
dc.date.issued2011-05-01en
dc.description.abstractThe targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas’ disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ,2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts.en
dc.description.versionPublished versionen
dc.format.extent? - ? (13) page(s)en
dc.identifier.doihttps://doi.org/10.1371/journal.pntd.0001023en
dc.identifier.issn1935-2727en
dc.identifier.issue5en
dc.identifier.orcidMackey, ZB [0000-0002-4533-0973]en
dc.identifier.urihttp://hdl.handle.net/10919/83437en
dc.identifier.volume5en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000291099100004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectInfectious Diseasesen
dc.subjectParasitologyen
dc.subjectTropical Medicineen
dc.subjectCYSTEINE PROTEASE INHIBITORSen
dc.subjectPLASMODIUM-FALCIPARUMen
dc.subjectTRYPANOSOMA-BRUCEIen
dc.subjectCHAGAS-DISEASEen
dc.subjectVINYL SULFONESen
dc.subjectMOUSE MODELen
dc.subjectIN-VITROen
dc.subjectDISCOVERYen
dc.subjectCRUZIen
dc.subjectMALARIAen
dc.titleMining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leadsen
dc.title.serialPLoS Neglected Tropical Diseasesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Facultyen

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