Cleavage and isomerization of RNA phosphodiester bonds: Nucleoside phosphotriesters and chimeric ribo/2 '-O-methylribo oligonucleotides as tools for mechanistic studies

: Mikkola S, Kosonen M, Lonnberg H

Publisher: BENTHAM SCIENCE PUBL LTD

: 2002

: Current Organic Chemistry

: CURRENT ORGANIC CHEMISTRY

: CURR ORG CHEM

: 6

: 523

: 538

: 16

: 1385-2728

DOI: https://doi.org/10.2174/1385272024604934

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.

Chemical sciences