Metal ion-promoted cleavage of mRNA 5′-cap models: hydrolysis of the triphosphate bridge and reactions of the N7-methylguanine base

Abstract

Reactions of mRNA 5′-cap model compounds were studied to evaluate the potential of these reactions in the development of artificial RNases. Diadenosine triphosphate was used as a model for the triphosphate bridge, and its hydrolysis was studied in the presence of several Cu²⁺ complexes. The results of the kinetic experiments show that bifunctional catalysis by phosphate bound Cu²⁺ complexes is involved. The most efficient catalysis is achieved with complexes with acidic aqua ligands, and a metal ion-bound hydroxo ligand most probably acts as a nucleophile in the reaction. A detailed mechanism cannot, however, be suggested on the basis of the data. N⁷-methylguanosine and its 5′-monophosphate and diphosphate were used to study the reactions of the N⁷-methylguanine base of the mRNA 5′-cap moiety. While Cu²⁺ complexes efficiently enhance the hydrolysis of the triphosphate bridge, little effect on the reactions of the N⁷-methylguanine base was observed: neither the cleavage of the imidazole ring or the depurination of the nucleoside were enhanced to any significant extent.