Refereed review article in scientific journal (A2)
Cleavage and isomerization of RNA phosphodiester bonds: Nucleoside phosphotriesters and chimeric ribo/2 '-O-methylribo oligonucleotides as tools for mechanistic studies
List of Authors: Mikkola S, Kosonen M, Lonnberg H
Publisher: BENTHAM SCIENCE PUBL LTD
Publication year: 2002
Journal: Current Organic Chemistry
Journal name in source: CURRENT ORGANIC CHEMISTRY
Journal acronym: CURR ORG CHEM
Volume number: 6
Issue number: 6
Start page: 523
End page: 538
Number of pages: 16
ISSN: 1385-2728
DOI: http://dx.doi.org/10.2174/1385272024604934
Abstract
Phosphodiester bonds of RNA undergo in aqueous solution two intramolecular transesterification reactions: cleavage to a cyclic 2',3'-phosphate and isomerization to a 2',5'-phosphodiester. The reaction is initiated by a nucleophilic attack of the 2'-hydroxy group on the phosphate, which results in formation of a pentacoordinated phosphorane species. This phosphorane intermediate may then decompose to either the cleavage or isomerization products. The reaction system is subject to several different type of catalysis, and under given conditions, different mechanisms may be concurrently utilized. The present review discusses the approaches where nucleoside 3'-phosphotriesters have been used as a model for the neutral ionic form of phosphodiesters to elucidate the mechanistic details of the transesterification of RNA phosphodiester bonds. Transesterification of the phosphodiester bonds within oligonucleotidic substrates is also influenced by the molecular environment of the scissile bond. The secondary structure influences on the reactivity of RNA phosphodiester bonds either by retarding the rate of cleavage or enhancing it. These effects are discussed in the light of the mechanisms described above.
Phosphodiester bonds of RNA undergo in aqueous solution two intramolecular transesterification reactions: cleavage to a cyclic 2',3'-phosphate and isomerization to a 2',5'-phosphodiester. The reaction is initiated by a nucleophilic attack of the 2'-hydroxy group on the phosphate, which results in formation of a pentacoordinated phosphorane species. This phosphorane intermediate may then decompose to either the cleavage or isomerization products. The reaction system is subject to several different type of catalysis, and under given conditions, different mechanisms may be concurrently utilized. The present review discusses the approaches where nucleoside 3'-phosphotriesters have been used as a model for the neutral ionic form of phosphodiesters to elucidate the mechanistic details of the transesterification of RNA phosphodiester bonds. Transesterification of the phosphodiester bonds within oligonucleotidic substrates is also influenced by the molecular environment of the scissile bond. The secondary structure influences on the reactivity of RNA phosphodiester bonds either by retarding the rate of cleavage or enhancing it. These effects are discussed in the light of the mechanisms described above.
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