Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity 英文参考文献.docVIP
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Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity 英文参考文献
FindingoftheLowMolecularWeightInhibitorsof
ResuscitationPromotingFactorEnzymaticand
ResuscitationActivity
GalinaR.Demina,VadimA.Makarov,VadimD.Nikitushkin,OlgaB.Ryabova,GalinaN.Vostroknutova,
ElenaG.Salina,MargaritaO.Shleeva,AnnaV.Goncharenko,ArsenyS.Kaprelyants*
A.N.BachInstituteofBiochemistry,RAS,Moscow,Russia
Abstract
Background:Resuscitationpromotingfactors(RPF)aresecretedproteinsinvolvedinreactivationofdormantactinobacteria,
includingMycobacteriumtuberculosis.Theyhavebeenconsideredasprospectivetargetsforthedevelopmentofnewanti-
tuberculosis drugs preventing reactivation of dormant tubercle bacilli, generally associated with latent tuberculosis.
However,noinhibitorsofRpfactivityhavebeenreportedsofar.Thegoalofthisstudywastofindlowmolecularweight
compoundsinhibitingtheenzymaticandbiologicalactivitiesofRpfs.
Methodology/Principal Findings: Here we describe a novel class of 2-nitrophenylthiocyanates (NPT) compounds that
inhibit muralytic activity of Rpfs with IC50 1–7mg/ml. Fluorescence studies revealed interaction of active NPTs with the
internalregionsoftheRpfmolecule.CandidateinhibitorsofRpfenzymaticactivityshowedabacteriostaticeffectongrowth
ofMicrococcusluteus(inwhichRpfisessentialforgrowthprotein)atconcentrationsclosetoIC .Thecandidatecompounds
50
suppressedresuscitationofdormant(‘‘non-culturable’’)cellsofM.smegmatisat1mg/mlordelayedresuscitationofdormant
M.tuberculosisobtainedinlaboratoryconditionsat10 mg/ml.However,theydidnotinhibitgrowthofactivemycobacteria
undertheseconcentrations.
Conclusions/Significance:NPTarethefirstexampleoflowmolecularweightcompoundsthatinhibittheenzymaticand
biologicalactivitiesofRpfproteins.
Citation:DeminaGR,MakarovVA,NikitushkinVD,RyabovaOB,VostroknutovaGN,etal.(2009)FindingoftheLowMolecularWeightInhibitorsofResuscitation
PromotingFactorEnzymaticandResuscitationActivity.PLoSONE4(12):e8174.doi:10.1371/journal.pone.0008174
Editor:KeertanDheda,UniversityofCapeTown,SouthAfrica
ReceivedJuly3,2009;AcceptedNovember8,2009;Publ
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