The synthesis and properties of tricyclic analogues of S6-methylthioguanine and O6-methylguanine.
The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of O(6)-methylguanine and S(6)-methylthioguanine are described. The crystal structures and pK(a) values of these analogues are reported. In a standard substrate assay with the human repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) only the oxygen-containing analogue displayed activity.
Hornillo-Araujo
Ana R
AR
Centre for Chemical Biology, Department of Chemistry, University of Sheffield, Sheffield, United Kingdom.
Burrell
Adam J M
AJ
Aiertza
Miren K
MK
Shibata
Takayuki
T
Hammond
David M
DM
Edmont
Dolorès
D
Adams
Harry
H
Margison
Geoffrey P
GP
Williams
David M
DM
D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D015394:Molecular Structure; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D006147:Guanine; C008449:O-(6)-methylguanine; D019853:O(6)-Methylguanine-DNA Methyltransferase