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dc.contributor.authorRead, M
dc.contributor.authorHarrison, RJ
dc.contributor.authorRomagnoli, B
dc.contributor.authorTanious, FA
dc.contributor.authorGowan, SH
dc.contributor.authorReszka, AP
dc.contributor.authorWilson, WD
dc.contributor.authorKelland, LR
dc.contributor.authorNeidle, S
dc.date.accessioned2018-09-26T10:24:41Z
dc.date.issued2001-04-24
dc.identifier9
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 pp. 4844 - 4849
dc.identifier.issn0027-8424
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2871
dc.identifier.doi10.1073/pnas.081560598
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.
dc.format.extent4844 - 4849
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.titleStructure-based design of selective and potent G quadruplex-mediated telomerase inhibitors
dc.typeJournal Article
rioxxterms.versionofrecord10.1073/pnas.081560598
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2001-04-24
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
pubs.notesunique-id: ISI:000168311500010
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume98
pubs.embargo.termsNot known
dc.contributor.icrauthorKelland, Lloyden
dc.contributor.icrauthorNeidle, Stephenen


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