Hydrolytic stability of 2 ',3 '-O-methyleneadenos-5 '-yl 2 ',5 '-di-O-methylurid-3 '-yl 5 '-O-methylurid-3 '(2 ')-yl phosphate: implications to feasibility of existence of phosphate-ranched RNA under physiological conditions



: Lonnberg T, Kiiski J, Mikkola S

Publisher: ROYAL SOC CHEMISTRY

: 2005

: Organic and Biomolecular Chemistry

: ORGANIC & BIOMOLECULAR CHEMISTRY

: ORG BIOMOL CHEM

: 3

: 6

: 1089

: 1096

: 8

: 1477-0520

DOI: https://doi.org/10.1039/b500054h(external)


Hydrolytic reactions of 2',3'-O-methyleneadenos-5'-yl 2', 5'-di-O-methylurid-3'-yl 5'-O-methylurid-3'(2')-yl phosphate (1a,b) have been followed by RP-HPLC over a wide pH range to evaluate the feasibility of occurrence of phosphate- branched RNA under physiological conditions. At pH < 2, where the decomposition of 1a, b is. rst order in [H3O+], the P-O5' bond is cleaved 1.5 times as rapidly as the P-O3' bond. Under these conditions, the reaction probably proceeds by an attack of the 2'-OH on the phosphotriester monocation. Over a relatively wide range from pH 2 to 5, the hydrolysis is pH-independent, referring to rapid initial deprotonation of the attacking 2'-OH followed by general acid catalyzed departure of the leaving nucleoside. The P-O5' bond is cleaved 3 times as rapidly as the P-O3' bond. At pH 6, the reaction becomes. rst order in [HO-], consistent with an attack of the 2 - oxyanion on neutral phosphate. The product distribution is gradually inversed: in 10 mmol L-1 aqueous sodium hydroxide, cleavage of the P-O3' bond is favored over P-O5' by a factor of 7.3. The results of the present study suggest that the half-life for the cleavage of 1a, b under physiological conditions is only 100 s. Even at pH 2, where 1a, b is most stable, the half-life for its cleavage is less than one hour and the isomerization between 1a and 1b is even more rapid than cleavage. The mechanisms of the partial reactions are discussed.



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