title: The syntheses and properties of tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6-methylthioguanine and O6-methylguanine.
abstract: The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6-methylthioguanine are described. The crystal structures and pKa values of these and related O6-methylguanine analogues are reported. All compounds display higher pKa values than O6-methylguanine with the sulfur-containing analogues being the more basic and exhibiting higher stability in aqueous solution. In a standard substrate assay with the human repair protein O6-methylguanine-DNA methyltransferase (MGMT) only the oxygen-containing analogue displayed activity.
authors.affiliation: Centre for Chemical Biology, Richard Roberts Building, Department of Chemistry, University of Sheffield, Brook Hill, UK.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Hornillo-Araujo
authors.forename: Adam J M
authors.initials: AJ
authors.lastname: Burrell
authors.forename: Miren K
authors.initials: MK
authors.lastname: Aiertza
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shibata
authors.forename: David M
authors.initials: DM
authors.lastname: Hammond
authors.forename: Dolorès
authors.initials: D
authors.lastname: Edmont
authors.forename: Harry
authors.initials: H
authors.lastname: Adams
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Margison
authors.forename: David M
authors.initials: DM
authors.lastname: Williams
mesh_terms: D018360:Crystallography, X-Ray; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis*; D011758:Pyrroles / Q000138:chemical synthesis*; D013379:Substrate Specificity; D013866:Thioguanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; C450639:Pyrrolo(2,3-d)pyrimidine; C035366:6-methylthioguanine; D006147:Guanine; C008449:O-(6)-methylguanine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013866:Thioguanine