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Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis

[Image: see text] Phosphoroimidazolides play a critical role in several enzymatic phosphoryl transfer reactions and have been studied extensively as activated monomers for nonenzymatic nucleic acid replication, but the detailed mechanisms of these phosphoryl transfer reactions remain elusive. Some a...

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Autores principales: Li, Li, Lelyveld, Victor S., Prywes, Noam, Szostak, Jack W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2016
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547882/
https://www.ncbi.nlm.nih.gov/pubmed/26974265
http://dx.doi.org/10.1021/jacs.6b00784
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author Li, Li
Lelyveld, Victor S.
Prywes, Noam
Szostak, Jack W.
author_facet Li, Li
Lelyveld, Victor S.
Prywes, Noam
Szostak, Jack W.
author_sort Li, Li
collection PubMed
description [Image: see text] Phosphoroimidazolides play a critical role in several enzymatic phosphoryl transfer reactions and have been studied extensively as activated monomers for nonenzymatic nucleic acid replication, but the detailed mechanisms of these phosphoryl transfer reactions remain elusive. Some aspects of the mechanism can be deduced by studying the hydrolysis reaction, a simpler system that is amenable to a thorough mechanistic treatment. Here we characterize the transition state of phosphoroimidazolide hydrolysis by kinetic isotope effect (KIE) and linear free energy relationship (LFER) measurements, and theoretical calculations. The KIE and LFER observations are best explained by calculated loose transition structures with extensive scissile bond cleavage. These three-dimensional models of the transition state provide the basis for future mechanistic investigations of phosphoroimidazolide reactions.
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spelling pubmed-75478822020-10-13 Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis Li, Li Lelyveld, Victor S. Prywes, Noam Szostak, Jack W. J Am Chem Soc [Image: see text] Phosphoroimidazolides play a critical role in several enzymatic phosphoryl transfer reactions and have been studied extensively as activated monomers for nonenzymatic nucleic acid replication, but the detailed mechanisms of these phosphoryl transfer reactions remain elusive. Some aspects of the mechanism can be deduced by studying the hydrolysis reaction, a simpler system that is amenable to a thorough mechanistic treatment. Here we characterize the transition state of phosphoroimidazolide hydrolysis by kinetic isotope effect (KIE) and linear free energy relationship (LFER) measurements, and theoretical calculations. The KIE and LFER observations are best explained by calculated loose transition structures with extensive scissile bond cleavage. These three-dimensional models of the transition state provide the basis for future mechanistic investigations of phosphoroimidazolide reactions. American Chemical Society 2016-03-14 2016-03-30 /pmc/articles/PMC7547882/ /pubmed/26974265 http://dx.doi.org/10.1021/jacs.6b00784 Text en This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Li, Li
Lelyveld, Victor S.
Prywes, Noam
Szostak, Jack W.
Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis
title Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis
title_full Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis
title_fullStr Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis
title_full_unstemmed Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis
title_short Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis
title_sort experimental and computational evidence for a loose transition state in phosphoroimidazolide hydrolysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547882/
https://www.ncbi.nlm.nih.gov/pubmed/26974265
http://dx.doi.org/10.1021/jacs.6b00784
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