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dc.contributor.authorRead, Men_US
dc.contributor.authorHarrison, RJen_US
dc.contributor.authorRomagnoli, Ben_US
dc.contributor.authorTanious, FAen_US
dc.contributor.authorGowan, SHen_US
dc.contributor.authorReszka, APen_US
dc.contributor.authorWilson, WDen_US
dc.contributor.authorKelland, LRen_US
dc.contributor.authorNeidle, Sen_US
dc.date.accessioned2018-09-26T10:24:41Z
dc.date.issued2001-04-24en_US
dc.identifier9en_US
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 pp. 4844 - 4849en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2871
dc.identifier.doi10.1073/pnas.081560598en_US
dc.description.abstractThe telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA, These 3,6,9-trisubstituted acridine inhibitors are predicted to interact selectively with the human DNA quadruplex structure, as a means of specifically inhibiting the action of human telomerase in extending the length of single-stranded telomeric: DNA. The anilino substituent at the 9-position of the acridine chromophore is predicted to lie in a third groove of the quadruplex. Calculated relative binding energies predict enhanced selectivity compared with earlier 3,6-disubstituted compounds, as a result of this substituent, The ranking order of energies is in accord with equilibrium binding constants for quadruplex measured by surface plasmon resonance techniques, which also show reduced duplex binding compared with the disubstituted compounds. The 3,6,9-trisubstututed acridines have potent in vitro inhibitory activity against human telomerase. with EC50 values of up to 60 nM.en_US
dc.format.extent4844 - 4849en_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.titleStructure-based design of selective and potent G quadruplex-mediated telomerase inhibitorsen_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1073/pnas.081560598en_US
rioxxterms.licenseref.startdate2001-04-24en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICAen_US
pubs.notesunique-id: ISI:000168311500010en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.volume98en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorKelland, Lloyden_US
dc.contributor.icrauthorNeidle, Stephenen_US


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