dc.contributor.author | Pettinger, J | |
dc.contributor.author | Le Bihan, Y-V | |
dc.contributor.author | Widya, M | |
dc.contributor.author | van Montfort, RLM | |
dc.contributor.author | Jones, K | |
dc.contributor.author | Cheeseman, MD | |
dc.date.accessioned | 2017-04-05T10:00:33Z | |
dc.date.issued | 2017-03-20 | |
dc.identifier.citation | Angewandte Chemie (International ed. in English), 2017, 56 (13), pp. 3536 - 3540 | |
dc.identifier.issn | 1433-7851 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/558 | |
dc.identifier.eissn | 1521-3773 | |
dc.identifier.doi | 10.1002/anie.201611907 | |
dc.description.abstract | The stress-inducible molecular chaperone, HSP72, is an important therapeutic target in oncology, but inhibiting this protein with small molecules has proven particularly challenging. Validating HSP72 inhibitors in cells is difficult owing to competition with the high affinity and abundance of its endogenous nucleotide substrates. We hypothesized this could be overcome using a cysteine-targeted irreversible inhibitor. Using rational design, we adapted a validated 8-N-benzyladenosine ligand for covalent bond formation and confirmed targeted irreversible inhibition. However, no cysteine in the protein was modified; instead, we demonstrate that lysine-56 is the key nucleophilic residue. Targeting this lysine could lead to a new design paradigm for HSP72 chemical probes and drugs. | |
dc.format | Print-Electronic | |
dc.format.extent | 3536 - 3540 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY-V C H VERLAG GMBH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | An Irreversible Inhibitor of HSP72 that Unexpectedly Targets Lysine-56. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-02-03 | |
rioxxterms.versionofrecord | 10.1002/anie.201611907 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Angewandte Chemie (International ed. in English) | |
pubs.issue | 13 | |
pubs.notes | No embargo | |
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 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 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-status | Published | |
pubs.volume | 56 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Medicinal Chemistry 3 | |
icr.researchteam | Hit Discovery & Structural Design | |
dc.contributor.icrauthor | Pettinger, Jonathan | |
dc.contributor.icrauthor | Le Bihan, Yann-Vai | |
dc.contributor.icrauthor | Van Montfort, Robert | |
dc.contributor.icrauthor | Jones, Keith | |
dc.contributor.icrauthor | Cheeseman, Matthew | |