Development of rationally designed DNA N6 adenine methyltransferase inhibitors

Bioorg Med Chem Lett. 2012 May 1;22(9):3079-82. doi: 10.1016/j.bmcl.2012.03.072. Epub 2012 Mar 27.


A series of bisubstrate inhibitors for DNA N6 adenine methyltransferase (Dam) have been synthesized by linking an amine analogue of S-adenosylmethionine to an aryl moiety designed to probe the binding pocket of the DNA adenine base. An initial structure-activity relationship study has identified substituents that increase inhibitor potency to the ∼10 μM range and improve selectivity against the human cytosine methyltransferase Dnmt1.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • S-Adenosylmethionine
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Substrate Specificity


  • Enzyme Inhibitors
  • S-Adenosylmethionine
  • Site-Specific DNA-Methyltransferase (Adenine-Specific)