The synthesis and properties of tricyclic analogues of S6-methylthioguanine and O6-methylguanine

Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):1099-102. doi: 10.1080/15257770701519221.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Guanine / analogs & derivatives*
  • Guanine / chemical synthesis
  • Guanine / chemistry
  • Guanine / pharmacology
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Molecular Structure
  • O(6)-Methylguanine-DNA Methyltransferase / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • Guanine
  • O-(6)-methylguanine
  • O(6)-Methylguanine-DNA Methyltransferase