Evidence map›Paper›PMID 21050838›Full record

ArticleAnalytical biochemistry2011

Design, synthesis, and evaluation of a new fluorescent probe for measuring polymyxin-lipopolysaccharide binding interactions.

Rachel L Soon, Tony Velkov, Francis Chiu, Philip E Thompson, Rashmi Kancharla, Kade Roberts, Ian Larson, Roger L Nation, Jian Li

Abstract readEvaluation Study
In one paragraph

Article in Analytical biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
0.8field-weighted citation impact, top 33% 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

30 citing papers in PubMed, 50 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Rachel L SoonMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Tony Velkov
Francis Chiu
Philip E Thompson
Rashmi Kancharla
Kade Roberts
Ian Larson
Roger L Nation
Jian Li
Monash University · AU

Funding

Optimizing Dosing of Colistin for Infections Resistant to all Other AntibioticsR01AI070896 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SILVEIRA, FERNANDA P. · 2007 to 2011
$3.6M
Targeting MDR hetero-resistant Gram-negatives: PK/PD for rational combinationsR01AI079330 · NIAID · MONASH UNIVERSITY · PI NATION, ROGER L. · 2008 to 2011
$2.2M
NIAID NIH HHS R01 AI070896NIAID NIH HHS R01 AI079330NIAID NIH HHS R01AI079330PHS HHS R01A1070896
6 · The paper itself

Abstract

Fluorescence assays employing semisynthetic or commercial dansyl-polymyxin B have been widely employed to assess the affinity of polycations, including polymyxins, for bacterial cells and lipopolysaccharide (LPS). The five primary γ-amines on diaminobutyric acid residues of polymyxin B are potentially derivatized with dansyl-chloride. Mass spectrometric analysis of the commercial product revealed a complex mixture of di- or tetra-dansyl-substituted polymyxin B. We synthesized a mono-substituted fluorescent derivative, dansyl[Lys]¹polymyxin B₃. The affinity of polymyxin for purified gram-negative LPS and whole bacterial cells was investigated. The affinity of dansyl[Lys]¹polymyxin B₃ for LPS was comparable to polymyxin B and colistin, and considerably greater (K(d)<1 μM) than for whole cells (K(d)∼6-12μM). Isothermal titration calorimetric studies demonstrated exothermic enthalpically driven binding between both polymyxin B and dansyl[Lys]¹polymyxin B₃ to LPS, attributed to electrostatic interactions. The hydrophobic dansyl moiety imparted a greater entropic contribution to the dansyl[Lys]¹polymyxin B₃-LPS reaction. Molecular modeling revealed a loss of electrostatic contact within the dansyl[Lys]¹polymyxin B₃-LPS complex due to steric hindrance from the dansyl[Lys]¹ fluorophore; this corresponded with diminished antibacterial activity (MIC≥16μg/mL). Dansyl[Lys]¹polymyxin B₃ may prove useful as a screening tool for drug development.

Indexed as

Binding SitesCalorimetryFluorescent DyesLipopolysaccharidesMass SpectrometryPhosphatidylcholinesPolymyxin BPolymyxins1-myristoyl-2-(12-((5-dimethylamino-1-naphthalenesulfonyl)amino)dodecanoyl)-sn-glycero-3-phosphocholineFluorescent DyesLipopolysaccharidesPhosphatidylcholinesPolymyxin Bpolymyxin B3, dansyllysyl(1)-Polymyxins

Identifiers

PMID21050838
PMCPMC3106281
OpenAlexW2074185445

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.