Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.

Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stefanie Kellner, Laura Bettina Kollar, Antonia Ochel, Manjunath Ghate, Mark Helm
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/821dda3b8b0a49af96dfb2e4d717bd8d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:821dda3b8b0a49af96dfb2e4d717bd8d
record_format	dspace
spelling	oai:doaj.org-article:821dda3b8b0a49af96dfb2e4d717bd8d2021-11-18T07:38:47ZStructure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.1932-620310.1371/journal.pone.0067945https://doaj.org/article/821dda3b8b0a49af96dfb2e4d717bd8d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23844135/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent labeling of RNA are developed as an attractive scaffold on which electronic properties can be modulated by varying the substituents. Six different 4-bromomethyl-coumarins of various substitution patterns were tested for nucleotide specificity of RNA alkylation using tRNA from Escherichia coli as substrate. Using semi-quantitative LC-MS/MS analysis, reactions at mildly acidic and slightly alkaline pH were compared. For all tested compounds, coumarin conjugates with 4-thiouridine, pseudouridine, guanosine, and uridine were identified, with the latter largely dominating. This data set shows that selectivity of ribonucleotide alkylation depends on the substitution pattern of the reactive dye, and even more strongly on the modulation of the reaction conditions. The latter should be therefore carefully optimized when striving to achieve selectivity. Interestingly, the highest selectivity for labeling of a modified nucleoside, namely of 4-thiouridine, was achieved with a compound whose selectivity was somewhat less dependent on reaction conditions than the other compounds. In summary, bromomethylcoumarin derivatives are a highly interesting class of compounds, since their selectivity for 4-thiouridine can be efficiently tuned by variation of substitution pattern and reaction conditions.Stefanie KellnerLaura Bettina KollarAntonia OchelManjunath GhateMark HelmPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67945 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stefanie Kellner Laura Bettina Kollar Antonia Ochel Manjunath Ghate Mark Helm Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.
description	Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent labeling of RNA are developed as an attractive scaffold on which electronic properties can be modulated by varying the substituents. Six different 4-bromomethyl-coumarins of various substitution patterns were tested for nucleotide specificity of RNA alkylation using tRNA from Escherichia coli as substrate. Using semi-quantitative LC-MS/MS analysis, reactions at mildly acidic and slightly alkaline pH were compared. For all tested compounds, coumarin conjugates with 4-thiouridine, pseudouridine, guanosine, and uridine were identified, with the latter largely dominating. This data set shows that selectivity of ribonucleotide alkylation depends on the substitution pattern of the reactive dye, and even more strongly on the modulation of the reaction conditions. The latter should be therefore carefully optimized when striving to achieve selectivity. Interestingly, the highest selectivity for labeling of a modified nucleoside, namely of 4-thiouridine, was achieved with a compound whose selectivity was somewhat less dependent on reaction conditions than the other compounds. In summary, bromomethylcoumarin derivatives are a highly interesting class of compounds, since their selectivity for 4-thiouridine can be efficiently tuned by variation of substitution pattern and reaction conditions.
format	article
author	Stefanie Kellner Laura Bettina Kollar Antonia Ochel Manjunath Ghate Mark Helm
author_facet	Stefanie Kellner Laura Bettina Kollar Antonia Ochel Manjunath Ghate Mark Helm
author_sort	Stefanie Kellner
title	Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.
title_short	Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.
title_full	Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.
title_fullStr	Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.
title_full_unstemmed	Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.
title_sort	structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of rna alkylation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/821dda3b8b0a49af96dfb2e4d717bd8d
work_keys_str_mv	AT stefaniekellner structurefunctionrelationshipofsubstitutedbromomethylcoumarinsinnucleosidespecificityofrnaalkylation AT laurabettinakollar structurefunctionrelationshipofsubstitutedbromomethylcoumarinsinnucleosidespecificityofrnaalkylation AT antoniaochel structurefunctionrelationshipofsubstitutedbromomethylcoumarinsinnucleosidespecificityofrnaalkylation AT manjunathghate structurefunctionrelationshipofsubstitutedbromomethylcoumarinsinnucleosidespecificityofrnaalkylation AT markhelm structurefunctionrelationshipofsubstitutedbromomethylcoumarinsinnucleosidespecificityofrnaalkylation
_version_	1718423172136566784

Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation.

Ejemplares similares