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dc.contributor.authorWheelhouse, Richard T.*
dc.contributor.authorBibby, Michael C.*
dc.contributor.authorNicolaou, Anna*
dc.contributor.authorPletsas, Dimitrios*
dc.date.accessioned2009-07-28T08:31:51Z
dc.date.available2009-07-28T08:31:51Z
dc.date.issued2009-07-28T08:31:51Z
dc.identifier.citationPletsas, D., Wheelhouse, R.T., Pletsas, V., Nicolaou, A., Jenkins, T.C., Bibby, M.C. and Kyrtopoulos, S.A. (). Polar, Functionalized Guanine-O6 Derivatives Resistant to Repair by O6-Alkylguanine-DNA Alkyltransferase: Implications for the Design of DNA-modifying Drugs. European Journal of Medicinal Chemistry.en
dc.identifier.urihttp://hdl.handle.net/10454/3168
dc.descriptionNoen
dc.description.abstractThe protein O6-alkylguanine-DNA alkyltransferase (Atase) is responsible for the repair of DNA lesions generated by several clinically important anti-cancer drugs; this is manifest as active resistance in those cancer cell lines proficient in Atase expression. Novel O6-substituted guanine analogues have been synthesized, bearing acidic, basic and hydrogen bonding functional groups. In contrast to existing O6-modified purine analogues, such as methyl or benzyl, the new compounds were found to resist repair by Atase even when tested at concentrations much higher than O6-benzylguanine, a well-established Atase substrate active both in vitro and in vivo. The inactivity of the new purines as covalent substrates for Atase indicates that agents to deliver these groups to DNA would represent a new class of DNA-modifying drug that circumvents Atase-mediated resistance.en
dc.language.isoenen
dc.subjectStructure activity relationen
dc.subjectGuanine derivativesen
dc.subjectCompetitive inhibitionen
dc.subjectPurine derivativesen
dc.subjectEnzyme inhibitoren
dc.subjectIn vitroen
dc.subjectChemical synthesisen
dc.subjectEnzymeen
dc.subjectTransferasesen
dc.subjectDNAen
dc.subjectRepairen
dc.titlePolar, Functionalized Guanine-O6 Derivatives Resistant to Repair by O6-Alkylguanine-DNA Alkyltransferase: Implications for the Design of DNA-modifying Drugs.en
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen
dc.identifier.doihttps://doi.org/10.1016/j.ejmech.2005.11.007


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