Metal ion complexes of macrocyclic polyamines enhance both the phosphate hydrolysis and imidazole ring opening of RNA 5 '-cap structure



: Zhang ZB, Lonnberg H, Mikkola S

Publisher: VERLAG HELVETICA CHIMICA ACTA AG

: 2005

: Chemistry and Biodiversity

: CHEMISTRY & BIODIVERSITY

: CHEM BIODIVERS

: 2

: 1

: 92

: 103

: 12

: 1612-1872

DOI: https://doi.org/10.1002/cbdv.200490169


The cleavage of P-1-(7-methylguanosyl-5') P-3-(guanosyl-5') triphosphate, a RNA 5'-cap model, by 2-hydroxyethyl- (6a-6c) and 2-aminoethyl-(7a-7c) substituted macrocycles in the presence and absence of Zn2+ and Cu2+ ions has been studied at pH 7.2 and 60degrees. In the presence of the metal ions, hydrolysis of the phosphate group is enhanced. The mono- and dinuclear Zn2+ complexes promote solely the phosphate hydrolysis, whereas the corresponding Cu2+ complexes accelerate both the phosphate hydrolysis and the imidazole ring opening of the 7-methylguanine base. In the absence of the metal ions, the macrocycles mainly promote breakdown of the 7-methylguanine base, most probably by enhancing the nucleophilic attack of hydroxide ion on the C(8)-atom by shielding the repulsive negative charge on the phosphate moiety. The 2-hydroxyethyl and 2-aminoethyl side arms exhibit a two- to three-fold rate acceleration. Opening of the imidazole ring eventually results in cleavage of the triphosphate bridge.



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