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dc.contributor.authorDamalanka, Vishnu C.
dc.contributor.authorKim, Yunjeong
dc.contributor.authorKankanamalage, Anushka C. Galasiti
dc.contributor.authorRathnayake, Athri D.
dc.contributor.authorMehzabeen, Nurjahan
dc.contributor.authorBattaile, Kevin P.
dc.contributor.authorLovell, Scott
dc.contributor.authorNguyen, Harry Nhat
dc.contributor.authorLushington, Gerald H.
dc.contributor.authorChang, Kyeong-Ok
dc.contributor.authorGroutas, William C.
dc.date.accessioned2018-04-22T20:31:48Z
dc.date.available2018-04-22T20:31:48Z
dc.date.issued2018-01-01
dc.identifier.citationDamalanka, Vishnu C.; Kim, Yunjeong; Kankanamalage, Anushka C. Galasiti; Rathnayake, Athri D.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Nguyen, Harry Nhat; Lushington, Gerald H.; Chang, Kyeong-Ok; Groutas, William C. 2018. Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease. European Journal of Medicinal Chemistry, vol. 143:pp 881-890en_US
dc.identifier.issn0223-5234
dc.identifier.otherWOS:000428216700072
dc.identifier.urihttp://dx.doi.org/10.1016/j.ejmech.2017.12.014
dc.identifier.urihttp://hdl.handle.net/10057/14949
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractAcute nonbacterial gastroenteritis caused by noroviruses constitutes a global public health concern and a significant economic burden. There are currently no small molecule therapeutics or vaccines for the treatment of norovirus infections. A structure-guided approach was utilized in the design of a series of inhibitors of norovirus 3CL protease that embody an oxazolidinone ring as a novel design element for attaining optimal binding interactions. Low micromolar cell-permeable inhibitors that display ant-inorovirus activity have been identified. The mechanism of action, mode of binding, and structural rearrangements associated with the interaction of the inhibitors and the enzyme were elucidated using X-ray crystallography.en_US
dc.description.sponsorshipNational Institutes of Health (AI109039) is gratefully acknowledged. Use of the University of Kansas Protein Structure Laboratory was supported by a grant from the National Institute of General Medical Sciences (P30GM110761) of the National Institutes of Health. Use of the IMCA-CAT beamline 17-ID at the Advanced Photon Source was supported by the companies of the Industrial Macromolecular 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 no. DE-AC02-06CH11357.en_US
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesEuropean Journal of Medicinal Chemistry;v.143
dc.subjectTransition-state inhibitorsen_US
dc.subjectData qualityen_US
dc.subjectMacromolecular crystallographyen_US
dc.subjectMacrocyclic inhibitorsen_US
dc.subjectSubstrate-specificityen_US
dc.subjectNorwalk-virusen_US
dc.subjectDiscoveryen_US
dc.subjectTherapeuticsen_US
dc.subjectReceptoren_US
dc.subjectTargetsen_US
dc.titleStructure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL proteaseen_US
dc.typeArticleen_US
dc.rights.holder© 2017 Elsevier Masson SAS. All rights reserved.en_US


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