Hydrolysis of 2 ',3 '-O-methyleneadenos-5 '-yl bis(2 ',5 '-di-O-methylurid-3 '-yl) phosphate, a sugar O-alkylated trinucleoside 3 ',3 ',5 '-monophosphate: Implications for the mechanism of large ribozymes



: Lonnberg T, Mikkola S

Publisher: AMER CHEMICAL SOC

: 2004

: Journal of Organic Chemistry

: JOURNAL OF ORGANIC CHEMISTRY

: J ORG CHEM

: 69

: 3

: 802

: 810

: 9

: 0022-3263

DOI: https://doi.org/10.1021/jo035094k(external)


Hydrolytic reactions of 2',3'-O-methyleneadenos-5'-yl bis(2',5'-di-O-methylurid-3'-yl) phosphate (1), a sugar O-alkylated trinucleoside 3',3',5'-monophosphate, have been followed by RP HPLC over a wide pH range. Under neutral and mildly acidic conditions, the only reaction observed was a pH-independent cleavage of the O-C5' bond of the 5'-linked nucleoside. Under more alkaline conditions nucleophilic attack by hydroxide ion starts to compete. The reaction is first order in [OH-] and becomes predominant at pH 10. Each of the 3'-linked nucleosides is displaced 2.9 times as readily as the 5'-linked one. To determine the 1, value for the hydroxide ion catalyzed hydrolysis of 1, two diesters (2a,b) having 2',3'-O-methyleneadenosine (7) and 2',5'-di-O-methyluridine (4) as leaving groups were hydrolyzed under alkaline conditions. Since the beta(1g) value for this reaction is known, DeltapK(a) between 4 and 7 could be calculated. The beta(1g) for the hydrolysis of 1 was estimated to be -0.5 with use of this information. The mechanisms of the partial reactions and the role of leaving group properties in ribozyme reactions of large ribozymes are discussed.



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