Oxadiazole-based cell permeable macrocyclic transition state inhibitors of norovirus 3CL protease

dc.contributor.authorDamalanka, Vishnu C.
dc.contributor.authorKim, Yunjeong
dc.contributor.authorAlliston, Kevin R.
dc.contributor.authorWeerawarna, Pathum M.
dc.contributor.authorKankanamalage, Anushka C. Galasiti
dc.contributor.authorLushington, Gerald H.
dc.contributor.authorMehzabeen, Nurjahan
dc.contributor.authorBattaile, Kevin P.
dc.contributor.authorLovell, Scott
dc.contributor.authorChang, Kyeong-Ok
dc.contributor.authorGroutas, William C.
dc.date.accessioned2016-04-22T15:30:33Z
dc.date.available2016-04-22T15:30:33Z
dc.date.issued2016-03-10
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractHuman noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease.en_US
dc.description.sponsorshipNational Institutes of Health (Grant R01 AI109039) is gratefully acknowledged. Use of the University of Kansas Protein Structure Laboratory was supported by grants from the National Center for Research Resources (Grant 5P20RR017708-10) and the National Institute of General Medical Sciences (Grant 8P20GM103420-10). Use of the IMCA-CAT beamline 17-ID at the Advanced Photon Source was supported by the companies of the Industrial Macro molecular Crystallography Association through a contract with Hauptman-Woodward Medical Research Institute. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract DE-AC02-06CH11357.en_US
dc.identifier.citationVishnu C. Damalanka, Yunjeong Kim, Kevin R. Alliston, Pathum M. Weerawarna, Anushka C. Galasiti Kankanamalage, Gerald H. Lushington, Nurjahan Mehzabeen, Kevin P. Battaile, Scott Lovell, Kyeong-Ok Chang, and William C. Groutas. Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease. Journal of Medicinal Chemistry 2016 59 (5), 1899-1913en_US
dc.identifier.issn0022-2623
dc.identifier.otherWOS:000372043400018
dc.identifier.urihttp://dx.doi.org/10.1021/acs.jmedchem.5b01464
dc.identifier.urihttp://hdl.handle.net/10057/12021
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofseriesJournal of Medicinal Chemistry;v.59:no.5
dc.rights.holderCopyright © 2016 American Chemical Societyen_US
dc.subjectRecognize beta-strandsen_US
dc.subjectNorwalk-virusen_US
dc.subjectSubstrate-specificityen_US
dc.subjectData qualityen_US
dc.subjectMacromolecular crystallographyen_US
dc.subjectMembrane-permeabilityen_US
dc.subjectPotent inhibitionen_US
dc.subject3c-like proteasesen_US
dc.subjectDrug discoveryen_US
dc.subjectActive-sitesen_US
dc.titleOxadiazole-based cell permeable macrocyclic transition state inhibitors of norovirus 3CL proteaseen_US
dc.typeArticleen_US
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