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dc.contributor.authorMohan, Sankaren_US
dc.contributor.authorMcAtamney, Sarahen_US
dc.contributor.authorHaselhorst, Thomasen_US
dc.contributor.authorvon Itzstein, Marken_US
dc.contributor.authorPinto, Brian Marioen_US
dc.description.abstractWe report here the exploitation of the 150-cavity in the active sites of group-1 neuraminidases for the design of new triazole-containing carbocycles related to oseltamivir. Inhibition studies with virus-like particles (VLPs) containing the influenza virus neuraminidase-1 (N1) activity indicate that several candidates are inhibitors, with Ki values in the 10-5-10-8 M range. In contrast, a known candidate that preserves the free amino group and a new candidate containing a guanidine function are better inhibitors, with Ki values of 1.5 נ10-9 and 4.6 נ10-10 M, respectively. The most active inhibitor of the N1 enzyme in the triazole series was selective for the N1 class and showed significantly less inhibition (Ki = 2.6 占vs 0.07 卩 of the free influenza virus neuraminidase-2 (N2). In addition, saturation transfer difference (STD) NMR spectroscopic studies with this compound and the VLPs show that the entire molecule forms contacts with residues in the active site. These data taken together support our proposed binding mode in which the active site and the adjoining 150-cavity are both occupied.en_US
dc.publisherAmerican Chemical Societyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalJournal of Medicinal Chemistryen_US
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry not elsewhere classifieden_US
dc.titleCarbocycles Related to Oseltamivir as Influenza Virus Group-1-Specific Neuraminidase Inhibitors. Binding to N1 Enzymes in the Context of Virus-like Particlesen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.en_AU
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