Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Guanine / analogs & derivatives*
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Guanine / chemical synthesis
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Guanine / chemistry
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Guanine / pharmacology
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Humans
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In Vitro Techniques
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Kinetics
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Molecular Structure
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O(6)-Methylguanine-DNA Methyltransferase / antagonists & inhibitors
Substances
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Enzyme Inhibitors
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Guanine
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O-(6)-methylguanine
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O(6)-Methylguanine-DNA Methyltransferase