A1 Refereed original research article in a scientific journal
Metal ion-dependent hydrolysis of RNA phosphodiester bonds within hairpin loops. A comparative kinetic study on chimeric ribo/2 '-O-methylribooligonucleotides
Authors: Zagorowska I, Kuusela S, Lonnberg H
Publisher: OXFORD UNIV PRESS
Publication year: 1998
Journal: Nucleic Acids Research
Journal name in source: NUCLEIC ACIDS RESEARCH
Journal acronym: NUCLEIC ACIDS RES
Volume: 26
Issue: 14
First page : 3392
Last page: 3396
Number of pages: 5
ISSN: 0305-1048
DOI: https://doi.org/10.1093/nar/26.14.3392
Abstract
Several chimeric ribo/2'-O-methylribo oligonucleotides were synthesized and their hydrolytic cleavage studied in the presence of Mg2+, Zn2+, Pb2+ and the 1,4,9-triazacyclododecane chelate of Zn2+ (Zn2+[12]aneN(3)) to evaluate the importance of RNA secondary structure as a factor determining the reactivity of phosphodiester bonds. In all the cases studied, a phosphodiester bond within a 4-7 nt loop was hydrolytically more stable than a similar bond within a linear single strand, but markedly less stable than that in a double helix. With Zn2+ and Zn2+[12]aneN(3), the hydrolytic stability of a phosphodiester bond within a hairpin loop gradually decreased on increasing the distance from the stem. A similar but less systematic trend was observed with Pb2+. Zn2+- and Pb2+-promoted cleavage was observed to be considerably more sensitive to the secondary structure of the chain than that induced by Zn2+[12]aneN(3). This difference in behaviour may be attributed to bidentate binding of uncomplexed aquo ions to two different phosphodiester bonds. Mg2+ was observed to be catalytically virtually inactive compared with the other cleaving agents studied.
Several chimeric ribo/2'-O-methylribo oligonucleotides were synthesized and their hydrolytic cleavage studied in the presence of Mg2+, Zn2+, Pb2+ and the 1,4,9-triazacyclododecane chelate of Zn2+ (Zn2+[12]aneN(3)) to evaluate the importance of RNA secondary structure as a factor determining the reactivity of phosphodiester bonds. In all the cases studied, a phosphodiester bond within a 4-7 nt loop was hydrolytically more stable than a similar bond within a linear single strand, but markedly less stable than that in a double helix. With Zn2+ and Zn2+[12]aneN(3), the hydrolytic stability of a phosphodiester bond within a hairpin loop gradually decreased on increasing the distance from the stem. A similar but less systematic trend was observed with Pb2+. Zn2+- and Pb2+-promoted cleavage was observed to be considerably more sensitive to the secondary structure of the chain than that induced by Zn2+[12]aneN(3). This difference in behaviour may be attributed to bidentate binding of uncomplexed aquo ions to two different phosphodiester bonds. Mg2+ was observed to be catalytically virtually inactive compared with the other cleaving agents studied.
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