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dc.contributor.authorCheeseman, MD
dc.contributor.authorWestwood, IM
dc.contributor.authorBarbeau, O
dc.contributor.authorRowlands, M
dc.contributor.authorDobson, S
dc.contributor.authorJones, AM
dc.contributor.authorJeganathan, F
dc.contributor.authorBurke, R
dc.contributor.authorKadi, N
dc.contributor.authorWorkman, P
dc.contributor.authorCollins, I
dc.contributor.authorvan Montfort, RLM
dc.contributor.authorJones, K
dc.date.accessioned2016-11-24T14:04:56Z
dc.date.issued2016-05-11
dc.identifier.citationJournal of medicinal chemistry, 2016, 59 (10), pp. 4625 - 4636
dc.identifier.issn0022-2623
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/286
dc.identifier.eissn1520-4804
dc.identifier.doi10.1021/acs.jmedchem.5b02001
dc.description.abstractHSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner.
dc.formatPrint-Electronic
dc.format.extent4625 - 4636
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectAdenosine
dc.subjectCrystallography, X-Ray
dc.subjectMolecular Conformation
dc.subjectStructure-Activity Relationship
dc.subjectDose-Response Relationship, Drug
dc.subjectModels, Molecular
dc.subjectHSP70 Heat-Shock Proteins
dc.titleExploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.
dc.typeJournal Article
dcterms.dateAccepted2016-04-26
rioxxterms.versionofrecord10.1021/acs.jmedchem.5b02001
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-05-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of medicinal chemistry
pubs.issue10
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 2
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 2
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
pubs.publication-statusPublished
pubs.volume59
pubs.embargo.termsNot known
icr.researchteamMedicinal Chemistry 2en_US
icr.researchteamMedicinal Chemistry 3en_US
icr.researchteamHit Discovery & Structural Designen_US
dc.contributor.icrauthorBurke, Rosemaryen
dc.contributor.icrauthorCheeseman, Matthewen
dc.contributor.icrauthorVan Montfort, Roberten
dc.contributor.icrauthorWorkman, Paulen
dc.contributor.icrauthorCollins, Ianen
dc.contributor.icrauthorJones, Keithen


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