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Phosphodiester models for cleavage of nucleic acids

Authors :
Satu Mikkola
Tuomas Lönnberg
Harri Lönnberg
Source :
Beilstein Journal of Organic Chemistry, Vol 14, Iss 1, Pp 803-837 (2018)
Publication Year :
2018
Publisher :
Beilstein-Institut, 2018.

Abstract

Nucleic acids that store and transfer biological information are polymeric diesters of phosphoric acid. Cleavage of the phosphodiester linkages by protein enzymes, nucleases, is one of the underlying biological processes. The remarkable catalytic efficiency of nucleases, together with the ability of ribonucleic acids to serve sometimes as nucleases, has made the cleavage of phosphodiesters a subject of intensive mechanistic studies. In addition to studies of nucleases by pH-rate dependency, X-ray crystallography, amino acid/nucleotide substitution and computational approaches, experimental and theoretical studies with small molecular model compounds still play a role. With small molecules, the importance of various elementary processes, such as proton transfer and metal ion binding, for stabilization of transition states may be elucidated and systematic variation of the basicity of the entering or departing nucleophile enables determination of the position of the transition state on the reaction coordinate. Such data is important on analyzing enzyme mechanisms based on synergistic participation of several catalytic entities. Many nucleases are metalloenzymes and small molecular models offer an excellent tool to construct models for their catalytic centers. The present review tends to be an up to date summary of what has been achieved by mechanistic studies with small molecular phosphodiesters.

Details

Language :
English
ISSN :
18605397
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Beilstein Journal of Organic Chemistry
Publication Type :
Academic Journal
Accession number :
edsdoj.3e1e619db474689a2ddbe143e6f275d
Document Type :
article
Full Text :
https://doi.org/10.3762/bjoc.14.68