Source:http://linkedlifedata.com/resource/pubmed/id/14510594
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2003-9-26
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pubmed:abstractText |
In this work we describe a high-throughput screening approach based on electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR) that rapidly interrogates the noncovalent interaction between RNA-based drug targets and components derived from a bacterial natural product library. The screening process detects molecules present in the natural product library that bind to a synthetic RNA target that mimics the prokaryotic 16S rRNA A-site, while simultaneously measuring specificity for the synthetic A-site target using a control RNA target that lacks the critical structural element of the A-site construct. This screening approach known as multitarget affinity/specificity screening (MASS) demonstrated the expected binding of paromomycin from a fractionated natural product library derived from Streptomyces rimosus sp. paromomycinus. A new molecule was observed to bind with specificity to the 16S A-site RNA construct. MS/MS characterization of this species yielded partial structural information suggesting it is an aminoglycoside consisting of a paromomycin core with one or more modified rings. This work demonstrates the tremendous utility of MASS for screening natural product fractions against macromolecular targets.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0163-3864
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
66
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1186-90
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:14510594-Base Sequence,
pubmed-meshheading:14510594-Biological Agents,
pubmed-meshheading:14510594-Escherichia coli,
pubmed-meshheading:14510594-Nucleic Acid Conformation,
pubmed-meshheading:14510594-Paromomycin,
pubmed-meshheading:14510594-RNA, Bacterial,
pubmed-meshheading:14510594-RNA, Ribosomal,
pubmed-meshheading:14510594-Spectrometry, Mass, Electrospray Ionization,
pubmed-meshheading:14510594-Streptomyces
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pubmed:year |
2003
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pubmed:articleTitle |
Multitarget affinity/specificity screening of natural products: finding and characterizing high-affinity ligands from complex mixtures by using high-performance mass spectrometry.
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pubmed:affiliation |
Ibis Therapeutics, a Division of Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, California 92008, USA.
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pubmed:publicationType |
Journal Article
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