Linked Life Data

21050838

Source:http://linkedlifedata.com/resource/pubmed/id/21050838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-23
pubmed:abstractText
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 ?-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 B?. The affinity of polymyxin for purified gram-negative LPS and whole bacterial cells was investigated. The affinity of dansyl[Lys]¹polymyxin B? for LPS was comparable to polymyxin B and colistin, and considerably greater (K(d)<1 ?M) than for whole cells (K(d)?6-12?M). Isothermal titration calorimetric studies demonstrated exothermic enthalpically driven binding between both polymyxin B and dansyl[Lys]¹polymyxin B? to LPS, attributed to electrostatic interactions. The hydrophobic dansyl moiety imparted a greater entropic contribution to the dansyl[Lys]¹polymyxin B?-LPS reaction. Molecular modeling revealed a loss of electrostatic contact within the dansyl[Lys]¹polymyxin B?-LPS complex due to steric hindrance from the dansyl[Lys]¹ fluorophore; this corresponded with diminished antibacterial activity (MIC?16?g/mL). Dansyl[Lys]¹polymyxin B? may prove useful as a screening tool for drug development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1096-0309
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
409
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-83
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Design, synthesis, and evaluation of a new fluorescent probe for measuring polymyxin-lipopolysaccharide binding interactions.
pubmed:affiliation
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies, Research Support, N.I.H., Extramural