Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Mikkola, Satu, Lönnberg, Tuomas, Lönnberg, Harri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2018
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
_version_ 1783315232274251776
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
work_keys_str_mv AT mikkolasatu phosphodiestermodelsforcleavageofnucleicacids
AT lonnbergtuomas phosphodiestermodelsforcleavageofnucleicacids
AT lonnbergharri phosphodiestermodelsforcleavageofnucleicacids