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dc.contributor.authorMahon, Brian P
dc.contributor.authorLomelino, Carrie L
dc.contributor.authorLadwig, Janina
dc.contributor.authorRankin, Gregory M
dc.contributor.authorDriscoll, Jenna M
dc.contributor.authorSalguero, Antonieta L
dc.contributor.authorPinard, Melissa A
dc.contributor.authorVullo, Daniela
dc.contributor.authorSupuran, Claudiu T
dc.contributor.authorPoulsen, Sally-Ann
dc.contributor.authorMcKenna, Robert
dc.date.accessioned2017-11-28T01:31:05Z
dc.date.available2017-11-28T01:31:05Z
dc.date.issued2015
dc.identifier.issn0022-2623
dc.identifier.doi10.1021/acs.jmedchem.5b00845
dc.identifier.urihttp://hdl.handle.net/10072/101460
dc.description.abstractInhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study, we present five X-ray crystal structures, determined to a resolution of 1.7 Å or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically “map” key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.relation.ispartofpagefrom6630
dc.relation.ispartofpageto6638
dc.relation.ispartofissue16
dc.relation.ispartofjournalJournal of Medicinal Chemistry
dc.relation.ispartofvolume58
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry not elsewhere classified
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchOrganic Chemistry
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode030499
dc.subject.fieldofresearchcode0304
dc.subject.fieldofresearchcode0305
dc.subject.fieldofresearchcode1115
dc.titleMapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX Using Structure-Activity Relationships of Glucosyl-Based Sulfamates
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorPoulsen, Sally-Ann
gro.griffith.authorMoeker, Janina
gro.griffith.authorRankin, Gregory


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