Collect. Czech. Chem. Commun. 2006, 71, 567-578

Kinetics of the Imidazolium Ring-Opening of mRNA 5'-cap Analogs in Aqueous Alkali

Alicja Stachelskaa,*, Zbigniew J. Wieczoreka, Janusz Stępińskib, Marzena Jankowska-Anyszkac, Harri Lönnbergd and Edward Darżynkiewiczb

a Department of Physics and Biophysics, University of Warmia and Mazury in Olsztyn, Oczapowskiego 4, 10-719 Olsztyn, Poland
b Department of Biophysics, Institute of Experimental Physics, Warsaw University, Żwirki i Wigury 93, 02-089 Warsaw, Poland
c Department of Chemistry, Warsaw University, 1 Pasteura, 02-093 Warsaw, Poland
d Department of Chemistry, University of Turku, 20014 Turku, Finland


Second-order rate constants for the hydroxide-ion-catalyzed imidazolium ring-opening of several mono- and dinucleosidic analogs of mRNA 5'-cap have been determined. Intramolecular stacking of the two nucleobases in the dinucleosidic analogs, m7GpppN (m7G = 7-methylguanosine, N = 5'-linked nucleoside), and electrostatic interaction between the N-alkylated imidazolium ring and phosphate moiety have been shown to shield the m7G moiety against the nucleophilic attack of hydroxide ion. In addition, the effect of methylation of the nucleobase amino groups and replacement of the 7-methyl group with other alkyl groups have been studied. The influence of all the structural modifications studied turned out to be modest, the cleavage rates of the most and least reactive analogs (with the exception of non-phosphorylated nucleosides) differing only by a factor of 5.

Keywords: Kinetics; Rate constants; cap Analogs; Dinucleoside phosphates; Imidazolium ring; Ionic strength; Nucleotides; mRNA; Purines.

References: 32 live references.