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Phosphodiester models for cleavage of nucleic acids
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Beilstein-Institut
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905247/ https://www.ncbi.nlm.nih.gov/pubmed/29719577 http://dx.doi.org/10.3762/bjoc.14.68 |
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author | Mikkola, Satu Lönnberg, Tuomas Lönnberg, Harri |
author_facet | Mikkola, Satu Lönnberg, Tuomas Lönnberg, Harri |
author_sort | Mikkola, Satu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5905247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-59052472018-05-01 Phosphodiester models for cleavage of nucleic acids Mikkola, Satu Lönnberg, Tuomas Lönnberg, Harri Beilstein J Org Chem Review 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. Beilstein-Institut 2018-04-10 /pmc/articles/PMC5905247/ /pubmed/29719577 http://dx.doi.org/10.3762/bjoc.14.68 Text en Copyright © 2018, Mikkola et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms) |
spellingShingle | Review Mikkola, Satu Lönnberg, Tuomas Lönnberg, Harri Phosphodiester models for cleavage of nucleic acids |
title | Phosphodiester models for cleavage of nucleic acids |
title_full | Phosphodiester models for cleavage of nucleic acids |
title_fullStr | Phosphodiester models for cleavage of nucleic acids |
title_full_unstemmed | Phosphodiester models for cleavage of nucleic acids |
title_short | Phosphodiester models for cleavage of nucleic acids |
title_sort | phosphodiester models for cleavage of nucleic acids |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905247/ https://www.ncbi.nlm.nih.gov/pubmed/29719577 http://dx.doi.org/10.3762/bjoc.14.68 |
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