Metal ion complexes of macrocyclic polyamines enhance both the phosphate hydrolysis and imidazole ring opening of RNA 5'-cap structure.
The cleavage of P1-(7-methylguanosyl-5') P3-(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 60 degrees. 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.
Zhang
Zhibo
Z
University of Turku, Department of Chemistry, FIN-20014 Turku.
Lönnberg
Harri
H
Mikkola
Satu
S
D003300:Copper / Q000737:chemistry*; D006868:Hydrolysis; D007093:Imidazoles / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000737:chemistry*; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D012315:RNA Caps / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D007093:Imidazoles; D007477:Ions; D047028:Macrocyclic Compounds; D010710:Phosphates; D011073:Polyamines; D012315:RNA Caps; D003300:Copper; D015032:Zinc