New Tripodal, “Supercharged” Analogues of Adenosine Nucleotides: Inhibitors for the Fhit Ap3A Hydrolase

Abstract

Methanetrisphosphonic acids provide a branch point for synthetic nucleotide analogues which can be exploited either to generate novel tripodal nucleotides or to incorporate additional negative charge into linear analogues relative to the parent nucleotide, as exemplified in the picture for ATP and diadenosine tetraphosphate (Ap4A). These compounds show valuable discriminatory behavior as competitive inhibitors for the tumor suppressor protein Fhit and a second ApnA pyrophosphohydrolase. X=H, Cl, F.