The stimulating adventure of KRN 7000.pdf

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1、Organic&BiomolecularChemistryCitethis:Org.Biomol.Chem.,2011,9,3080www.rsc.org/obcPERSPECTIVEThestimulatingadventureofKRN7000†AlineBanchet-Cadeddu,*aEricHenon,´aManuelDauchez,bJean-HuguesRenault,aFannyMonneauxcandArnaudHaudrechyaReceived3rdNovember2010,Accepted12thJanuary2011DOI:10.1039/c0ob00975jA

2、ssociatedwiththeCD1dprotein,KRN7000,apotentsynthetica-galactosylceramide,isknowntoactivatetheinvariantNKTimmunecells.ThisstimulationthenleadstotheproductionofdifferentcytokinesmodulatingaTH1/TH2immuneresponsebalanceinvolvedinprotectionagainstseveralpathologiessuchasautoimmunediseasesandcancers.Var

3、iouseffortshavebeenmadetowardthesynthesisofsimpleandmorefunctionalizedanaloguesinordertoselectivelyinduceTH1orTH2-typecytokineproduction.SincethediscoveryofKRN7000,structure-activityrelationships,crystallographicandmodellingstudieshavepointedtothepotentialofseveralGalCeranaloguesintermofselectiveb

4、ioactivity,andhavehighlightedinterestingelementsinordertobetterunderstandtherecognitionandactivationmechanismsofimmuneiNKTcells.Bypresentinganup-to-datelibraryofanalogues,collectingrecentbreakthroughsdoneincrystallographyandmolecularmodelling,andrelatingthemtotheavailablebiologicalresults,wehopeth

5、atthisreviewwillhighlightandhelpthescientificcommunityintheirKRNresearch.1.IntroductionaICMR-CNRSUMR6229,UniversitedeReimsChampagne-Ardenne,BP´Natureaboundswithanamazingamountofpotentiallybioactive1039,51687REIMScedex,France.E-mail:A.Banchet@laposte.net;Fax:+compoundsandhasalwaysarousedtheinteresto

6、fscientists.33(0)326913166(ICMR);Tel:+33(0)678619782MarineinvertebratesareknowntobeanimportantreservoirbMEDyC-CNRSUMR6237,UniversitedeReimsChampagne-Ardenne,BP´ofsuchmolecules.1Atthepresenttime,fewdrugsareac-1039,51687REIMScedex,Francectuallyderivedfrommarineorganisms,butseveralpromisingIBMC-CNRSU

7、PR9021,UniversitedeStrasbourg,67084STRASBOURG´moleculesarecurrentlyinpreclinical/clinicaltrials.2Sponges,cedex,France†DedicatedtothemembersofthefirstGlycoLipidEuropeanNetworkthesimplestandmostancientmulticellulara