Evidence map›Paper›PMID 19278238›Full record

ArticleACS chemical biology2009

Small molecule microarrays of RNA-focused peptoids help identify inhibitors of a pathogenic group I intron.

Lucas P Labuda, Alexei Pushechnikov, Matthew D Disney

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
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  4. Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Lucas P LabudaDepartment of Chemistry and The Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, 657 Natural Sciences Complex, Buffalo, NY 14260, USA.
Alexei Pushechnikov
Matthew D Disney
Buffalo Society of Natural Sciences · US

Funding

Identifying and Studying RNA Loop-Small Molecule InteractionsR01GM079235 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI DISNEY, MATTHEW D · 2008 to 2012
$2.6M
NIGMS NIH HHS R01 GM 079235NIGMS NIH HHS R01 GM079235
6 · The paper itself

Abstract

Peptoids that inhibit the group I intron RNA from Candida albicans, an opportunistic pathogen that kills immunocompromised hosts, have been identified using microarrays. The arrayed peptoid library was constructed using submonomers with moieties similar to ones found in small molecules known to bind RNA. Library members that passed quality control analysis were spotted onto a microarray and screened for binding to the C. albicans group I intron ribozyme. Each ligand binder identified from microarray-based screening inhibited self-splicing in the presence of 1 mM nucleotide concentration of bulk yeast tRNA with IC(50)'s between 150 and 2200 microM. The binding signals and the corresponding IC(50)'s were used to identify features in the peptoids that predispose them for RNA binding. After statistical analysis of the peptoids' structures that bind, a second generation of inhibitors was constructed using these important features; all second generation inhibitors have improved potencies with IC(50)'s of <100 microM. The most potent inhibitor is composed of one phenylguanidine and three tryptamine submonomers and has an IC(50) of 31 microM. This compound is 6-fold more potent than pentamidine, a clinically used drug that inhibits self-splicing. These results show that (i) modulators of RNA function can be identified by designing RNA-focused chemical libraries and screening them via microarray; (ii) statistical analysis of ligand binders can identify features in leads that predispose them for binding to their targets; and (iii) features can then be programmed into second generation inhibitors to design ligands with improved potencies.

Indexed as

AnimalsBinding SitesCandida albicansDose-Response Relationship, DrugIntronsLigandsMolecular ConformationOligonucleotide Array Sequence AnalysisPeptide LibraryPeptoidsPneumocystis cariniiRNA, CatalyticRNA, FungalRNA SplicingRNA, TransferTetrahymena thermophilaLigandsPeptide LibraryPeptoidsRNA, CatalyticRNA, FungalRNA, Transfer

Identifiers

PMID19278238
PMCPMC2777746
OpenAlexW343398272

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.