A1 Refereed original research article in a scientific journal
Metal ion-promoted cleavage of mRNA 5 '-cap models: hydrolysis of the triphosphate bridge and reactions of the N-7-methylguanine base
Authors: Valakoski S, Heiskanen S, Andersson S, Lahde M, Mikkola S
Publisher: ROYAL SOC CHEMISTRY
Publication year: 2002
Journal: Journal of the Chemical Society, Perkin Transactions 2
Journal name in source: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
Journal acronym: J CHEM SOC PERK T 2
Issue: 3
First page : 604
Last page: 610
Number of pages: 7
ISSN: 1472-779X
DOI: https://doi.org/10.1039/b108222a
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. N-7-methylguanosine and its 5'-monophosphate and diphosphate were used to study the reactions of the N-7-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 N-7-methylguanine base was observed: neither the cleavage of the imidazole ring or the depurination of the nucleoside were enhanced to any significant extent.