Leiuorotoxin-Dab7(Lei-Dab7)isamutatedversionofLeiurotoxin,apeptideidentifiedfromthevenomofthescorpionLeiurusquinquestriatushebraeus.TheDabaminoacidinposition7conferstothiscompoundahighselectivityforSK2channelsamongotherchannels.Lei-Dab7exhibits>200foldselectivityforSK2overSK1,SK3,IK,KvandKirchannels.TheIC50forSK2isabout3nM.
Description:
AAsequence:Ala-Phe-Cys3-Asn-Leu-Arg-Dab-Cys8-Gln-Leu-Ser-Cys12-Arg-Ser-Leu-Gly-Leu-Leu-Gly-Lys-Cys21-Ile-Gly-Asp-Lys-Cys26-Glu-Cys28-Val-Lys-His-NH2
Disulfidebondsbetween:Cys3-Cys21,Cys8-Cys26andCys12-Cys28
Length(aa):31
Formula: C141H236N46O39S6
MolecularWeight:3392.12Da
Appearance:Whitelyophilizedsolid
Solubility:waterandsalinebuffer
CASnumber:[1061556-49-7]Source:Synthetic
Purityrate:>95%
Reference:
Correspondencesbetweenthebindingcharacteristicsofanon-naturalpeptide,Lei-Dab7
Small-conductancecalcium-activatedpotassiumchannels(SK1-SK3channels)areresponsIBLeforlong-lastinghyperpolarizationfollowingactionpotentialandcontributetotheneuronalfiringandintegrationsignal.Twopeptidetoxins:apaminandLeiurotoxin1,blockthisSKchannelswithhighaffinities.WegeneratedamodifiedLeiurotoxin1(Lei-Dab7)thatinhibitsSK2channelswithahighselectivity.CompetitivebindingofrADIo-iodinatedapamintodifferentratbrainstructures,inthepresenceofnativeapaminandLei-Dab7,hasshownthatdissociationconstantsdifferbyafactorof1000andthusdemonstratedthatligandaffinityisasimportantasligandselectivityforaspecificreceptor.However,thelackofligandsdiscriminatingbetweenSKchannelsubunitsisimpedingtheunderstandingoftheroleofeachheteromericSKchanneltypeindifferenttissues.OurstudyaimstobetterunderstandthemolecularcombinationsofSKchannelsandtheirassociationwithspecificfunctionalimplications.Onthispurpose,aclusteringtechniqueallowsustoidentifyfivegroupsofbrainstructuresreflectingsingularprofilesofaffinityandselectivityofLei-Dab7incomparisonwithapamin.TheanalysisofcorrespondencesbetweenLei-Dab7bindinganddistributionofSKsubunitsinthesegroupsofbrainstructuressuggeststhatfunctionalheteromericSKchannelsareinvolvedinspecificinformationprocesses.
Aidi-KnaniS.,etal.(2015)Correspondencesbetweenthebindingcharacteristicsofanon-naturalpeptide,Lei-Dab7,andthedistributionofSKsubunitsintheratcentralnervoussystem.EurJPharmacol.PMID:25704615
Small-conductanceCa2+-activatedpotassiumtype2channelsregulatetheformationofcontextualfearmemory
MurthySR.,etal.(2015)Small-conductanceCa2+-activatedpotassiumtype2channelsregulatetheformationofcontextualfearmemory.PLoSOne.PMID:25938421
Smallconductancecalcium-activatedK+channels,SkCa,butnotvoltage-gatedK+(Kv)channels,areimplicatedintheantinociceptioninducedbyCGS21680,aA2Aadenosinereceptoragonist.
IthasbeenshownthatA2Aadenosinereceptorsareimplicatedinpainmodulation.TheprecisemechanismbywhichactivationofA2Areceptorsproducesanalgesiceffects,however,remainsunclear.Theaimofthisstudywastoinvestigatethepossibleinvolvementofapamin-sensitivecalcium-activatedpotassiumchannels(SKCa)andvoltage-gatedpotassium(Kv)channelsinA2Areceptoractivation-inducedanalgesiceffects.Usingmice,weevaluatedtheinfluenceofapamin,anonspecificblockerofSKCachannels,Lei-Dab7(ananalogofscorpionLeiurotoxin),aselectiveblockerofSKCa2channels,andkaliotoxin(KTX)aKvchannelblocker,ontheCGS21680(A2Aadenosinereceptoragonist)-inducedincreasesinhotplateandtailpinchlatencies.Alldrugswereinjectedinmiceviatheintracerebroventricularroute.WefoundthatapaminandLei-Dab7,butnotKTX,reducedantinociceptionproducedbyCGS21680onthehotplateandtailpinchtestsinadosedependentmanner.Lei-Dab7wasmorepotentthanapamininthisregard.WeconcludethatSKCabutnotKvchannelsareimplicatedinCGS21680-inducedantinociception.
RegayaI.,etal.(2004)Smallconductancecalcium-activatedK+channels,SkCa,butnotvoltage-gatedK+(Kv)channels,areimplicatedintheantinociceptioninducedbyCGS21680,aA2Aadenosinereceptoragonist.LifeSci.PMID:15530499
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