Margatoxin(MgTx)isacomponentofthevenomofScorpioCentruroidesmargaritatus.Margatoxinpreferentiallyinhibitsvoltage-dependentpotassiumchannelsKv1.3withanIC50valuearound50pM(20foldmorepotentthanCharyBDotoxin)andirreversIBLyinhibitstheproliferationresponseofhumanT-cellsat20µMconcentration.MargatoxinisknowntobelesspotentonKv1.3expressedinXenopusOocytes(IC50around1nM).MargatoxinwasalsodescribedtobeapotentinhibitorofhumanvascularsmoothmusclecellmigrationwithanIC50of85pM.
FreesampleDescription:
AAsequence:Thr-Ile-Ile-Asn-Val-Lys-Cys7-Thr-Ser-Pro-Lys-Gln-Cys13-Leu-Pro-Pro-Cys17-Lys-Ala-Gln-Phe-Gly-Gln-Ser-Ala-Gly-Ala-Lys-Cys29-Met-Asn-Gly-Lys-Cys34-Lys-Cys36-Tyr-Pro-His-OH
(DisulfidebondsbetweenCys7-Cys29,Cys13-Cys34andCys17-Cys36)
Length(aa):39
Formula:C178H286N52O50S7
MolecularWeight:4179.03Da
Appearance:Whitelyophilizedsolid
Solubility:waterandsalinebuffer
CASnumber:[145808-47-5]Source:Synthetic
Purityrate:>97%
Reference:
PotentsuppressionofvascularsmoothmusclecellmigrationandhumanneointimalhyperplasiabyKV1.3channelblockers
AIM:
TheaimofthestudywastodeterminethepotentialforK(V)1potassiumchannelblockersasinhibitorsofhumanneoinitimalhyperplasia.
METHODSANDRESULTS:
Bloodvesselswereobtainedfrompatientsormiceandstudiedinculture.Reversetranscriptase-polymerasechainreactionandimmunocytochemistrywereusedtodetectgeneexpression.Whole-cellpatch-clamp,intracellularcalciummeasurement,cellmigrationassays,andorganculturewereusedtoassesschannelfunction.K(V)1.3wasuniqueamongtheK(V)1channelsinshowingpreservedandup-regulatedexpressionwhenthevascularsmoothmusclecellsswitchedtotheproliferatingphenotype.Therewasstrongexpressioninneointimalformations.Voltage-dependentpotassiumcurrentinproliferatingcellswassensitivetothreedifferentblockersofK(V)1.3channels.Calciumentrywasalsoinhibited.Allthreeblockersreducedvascularsmoothmusclecellmigrationandtheeffectswerenon-additive.Oneoftheblockers(margatoxin)washighlypotent,suppressingcellmigrationwithanIC(50)of85pM.Twooftheblockersweretestedinorgan-culturedhumanveinsamplesandbothinhibitedneointimalhyperplasia.
CONCLUSION:
K(V)1.3potassiumchannelsarefunctionalinproliferatingmouseandhumanvascularsmoothmusclecellsandhavepositiveeffectsoncellmigration.Blockersofthechannelsmaybeusefulasinhibitorsofneointimalhyperplasiaandotherunwantedvascularremodellingevents.
CheongA.,etal.(2011)PotentsuppressionofvascularsmoothmusclecellmigrationandhumanneointimalhyperplasiabyKV1.3channelblockers.CardiovascRes.PMID20884640
Kv1.3channelsinpostganglionicsympatheticneurons:expression,function,andmodulation
DocziMA.etal.(2008)Kv1.3channelsinpostganglionicsympatheticneurons:expression,function,andmodulation.AmJPhysiolRegulIntegrCompPhysiol.PMID18614767
PotentsuppressionofKv1.3potassiumchannelandIL-2secretionbydiphenylphosphineoxide-1inhumanTcells
ZhaoN.,etal.(2013)PotentsuppressionofKv1.3potassiumchannelandIL-2secretionbydiphenylphosphineoxide-1inhumanTcells.PLoSOne.PMID23717641
TheeffectsofKv1.3andIKCa1potassiumchannelinhibitiononcalciuminfluxofhumanperipheralTlymphocytesinrheumatoidarthritis
OBJECTIVE:
Thetransientincreaseofthecytoplasmicfreecalciumlevelplaysakeyroleintheprocessoflymphocyteactivation.Kv1.3andIKCa1potassiumchannelsareimportantregulatorsofthemaintenanceofcalciuminfluxduringlymphocyteactivationandpresentapossibletargetforselectiveimmunomodulation.
DESIGN:
Case-controlstudy.
SUBJECTSANDMETHODS:
Wetookperipheralbloodsamplesfrom10healthyindividualsand9recentlydiagnosedrheumatoidarthritis(RA)patientsreceivingnoanti-rheumatictreatment.WeevaluatedcalciuminfluxkineticsfollowingactivationinCD4,Th1,Th2andCD8cellsapplyinganovelflowcytometryapproach.WealsoassessedthesensitivityoftheabovesubsetstospecificinhibitionoftheKv1.3andIKCa1potassiumchannels.
RESULTS:
ThepeakofcalciuminfluxinlymphocytesisolatedfromRApatientsisreachedmorerapidly,indicatingthattheyrespondmorequicklytostimulationcomparedtocontrols.Inhealthyindividuals,theinhibitionoftheIKCa1channeldecreasedcalciuminfluxinTh2andCD4cellstoalowerextentthaninTh1andCD8cells.Onthecontrary,theinhibitionofKv1.3channelsresultedinalargerdecreaseofcalciumentryinTh2andCD4thaninTh1andCD8cells.NodifferencewasdetectedbetweenTh1andTh2orCD4andCD8cellsinthesensitivitytoIKCa1channelinhibitionamonglymphocytesofRApatients.However,specificinhibitionoftheKv1.3channelactsdifferentiallyoncalciuminfluxkineticsinRAlymphocytesubsets.Th2andparticularlyCD8cellsareinhibitedmoredominantlythanTh1andCD4cells.
CONCLUSION:
TheinhibitionofKv1.3channelsdoesnotseemtobespecificenoughinperipheralRAlymphocytes,sinceanti-inflammatoryTh2cellsarealsoaffectedtoanoteworthyextent.
ToldiG.,etal.(2013)TheeffectsofKv1.3andIKCa1potassiumchannelinhibitiononcalciuminfluxofhumanperipheralTlymphocytesinrheumatoidarthritis.ImmunoBIOLOGy.PMID22705192
OverexpressionofDelayedRectifierK(+)ChannelsPromotesInsituProliferationofLeukocytesinRatKidneyswithAdvancedChronicRenalFailure
Leukocytes,suchaslymphocytesandmacrophages,predominantlyexpressdelayedrectifierK(+)channels(Kv1.3),andthechannelsplaycrucialrolesintheactivationandproliferationofthecells.Sincelymphocytesareactivatedinpatientswithend-stagerenaldisease(ESRD),thechannelsexpressedinthosecellswouldcontributetotheprogressionofrenalfibrosisinadvanced-stagechronicrenalfailure(CRF).Inthepresentstudy,usingaratmodelwithadvancedCRFthatunderwent5/6nephrectomyfollowedbya14-weekrecoveryperiod,weexaminedthehistopathologicalfeaturesofthekidneysandtheleukocyteexpressionofKv1.3-channelsandcellcycleMarkers.Age-matchedsham-operatedratswereusedascontrols.InthecorticalinterstitiumofadvancedCRFratkidneys,leukocytesproliferatedinsituandoverexpressedKv1.3channelproteinintheircytoplasm.Treatmentwithmargatoxin,aselectiveKv1.3-channelinhibitor,significantlysuppressedthenumberofleukocytesandtheprogressionofrenalfibrosiswithasignificantdecreaseinthecorticalcellcyclemarkerexpression.ThisstudydemonstratedforthefirsttimethatthenumberofleukocyteswasdramaticallyincreasedinratkidneyswithadvancedCRF.TheoverexpressionofKv1.3channelsintheleukocyteswasthoughttocontributetotheprogressionofrenalfibrosisbystimulatingcellcyclingandpromotingcellularproliferation.
KazamaI.,etal.(2012)OverexpressionofDelayedRectifierK(+)ChannelsPromotesInsituProliferationofLeukocytesinRatKidneyswithAdvancedChronicRenalFailure.IntJNephrol.PMID22701172
CharacteristicsofACh-inducedhyperpolarizationandrelaxationinrabbitjugularvein
BACKGROUNDANDPURPOSE:
Therolesplayedbyendothelium-derivedNOandprostacyclinandbyendothelialcellhyperpolarizationinACh-inducedrelaxationhavebeenwellcharacterizedinarteries.However,themechanismsunderlyingACh-inducedrelaxationinveinsremaintobefullyclarified.
EXPERIMENTALAPPROACH:
ACh-inducedsmoothmusclecell(SMC)hyperpolarizationandrelaxationweremeasuredinendothelium-intactand-denudedpreparationsofrabbitjugularvein.
KEYRESULTS:
Inendothelium-intactpreparations,ACh(≤10⁻⁸M)marginallyincreasedtheintracellularconcentrationofCa²⁺([Ca²⁺](i))inendothelialcellsbutdidnotaltertheSMCmembranepotential.However,ACh(10⁻¹⁰-10⁻⁸M)inducedaconcentration-dependentrelaxationduringthecontractioninducedbyPGF(2α)andthisrelaxationwasblockedbytheNOsynthaseinhibitorN(ω)-nitro-l-arginine.ACh(10⁻⁸-10⁻⁶M)concentration-dependentlyincreasedendothelial[Ca²⁺](i)andinducedSMChyperpolarizationandrelaxation.TheseSMCresponseswereblockedinthecombinedpresenceofapamin[blockerofsmall-conductanceCa²⁺-activatedK⁺(SK(Ca),K(Ca)2.3)channel],TRAM34[blockerofintermediate-conductanceCa²⁺-activatedK⁺(IK(Ca),K(Ca)3.1)channel]andmargatoxin[blockerofsubfamilyofvoltage-gatedK⁺(K(V))channel,K(V)1].
CONCLUSIONSANDIMPLICATIONS:
Inrabbitjugularvein,NOplaysaprimaryroleinendothelium-dependentrelaxationatverylowconcentrationsofACh(10⁻¹⁰-10⁻⁸M).Athigherconcentrations,ACh(10⁻⁸-3×10⁻⁶M)inducesSMChyperpolarizationthroughactivationofendothelialIK(Ca),K(V)1and(possibly)SK(Ca)channelsandproducesrelaxation.TheseresultsimplythatAChregulatesrabbitjugularveintonusthroughactivationoftwoendothelium-dependentregulatorymechanisms.
ItohT.etal.(2012)CharacteristicsofACh-inducedhyperpolarizationandrelaxationinrabbitjugularvein.BrJPharmacol.PMID22595036
Charybdotoxinandmargatoxinactingonthehumanvoltage-gatedpotassiumchannelhKv1.3anditsH399Nmutant:anexperimentalandcomputationalcomparison
Theeffectofthepore-blockingpeptidescharybdotoxinandmargatoxin,bothscorpiontoxins,oncurrentsthroughhumanvoltage-gatedhK(v)1.3wild-typeandhK(v)1.3_H399Nmutantpotassiumchannelswascharacterizedbythewhole-cellpatchclamptechnique.Inthemutantchannels,bothtoxinshardlyblockedcurrentthroughthechannels,althoughtheydidpreventC-typeinactivationbyslowingdownthecurrentdecayduringdepolarization.Moleculardynamicssimulationssuggestedthatthefastcurrentdecayinthemutantchannelwasaconsequenceofaminoacidreorientationsbehindtheselectivityfilterandindicatedthattherigidity-flexibilityinthatregionplayedakeyroleinitsinteractionswithscorpiontoxins.Achannelwithaslightlymoreflexibleselectivityfilterregionexhibitsdistinctinteractionswithscorpiontoxins.Ourstudiessuggestthatthetoxin-channelinteractionsmightpartiallyrestorerigidityintheselectivityfilterandtherebypreventthestructuralrearrangementsassociatedwithC-typeinactivation.
NikoueeA.etal.(2012)Charybdotoxinandmargatoxinactingonthehumanvoltage-gatedpotassiumchannelhKv1.3anditsH399Nmutant:anexperimentalandcomputationalcomparison.JPhysChemB.PMID22490327
Voltage-dependentbiphasiceffectsofchloroquineondelayedrectifierK(+)-channelcurrentsinmurinethymocytes
LymphocytesareofrichindelayedrectifierK(+)-channels(Kv1.3)intheirplasmamembranes,andthechannelsplaycrucialrolesinthelymphocyteactivationandproliferation.Sincechloroquine,awidelyusedanti-malarialdrug,exertsimmunosuppressiveeffects,itwillaffectthechannelcurrentsinlymphocytes.Inthepresentstudy,employingthestandardpatch-clampwhole-cellrecordingtechnique,weexaminedtheeffectsofchloroquineonthechannelsexpressedinmurinethymocytes.Publishedpapersreportthatchloroquinewillinhibitvoltage-dependentK(+)-channelcurrentsbypluggingintotheopen-pore.Weobserved,indeed,thatchloroquinesuppressedthepulse-endcurrentsofKv1.3-channelsathighervoltagesteps.Surprisingly,however,wefoundthatthedrugenhancedthepeakcurrentsatbothhigherandlowervoltagesteps.SincechloroquineshowedsuchbiphasiceffectsonthethymocyteK(+)-channels,andsincethoseeffectswerevoltagedependent,weexaminedtheeffectsofchloroquineontheactivationandtheinactivationofthechannelcurrents.Wenotedthatchloroquineshiftedboththeactivationandtheinactivationcurvestowardthehyperpolarizingpotential,andthatthoseshiftsweremoreemphasizedatlowervoltagesteps.WeconcludethatchloroquinefacilitatesboththeactivationandtheinactivationofKv1.3-channelcurrentsinthymocytes,andthatthoseeffectsarevoltagedependent.
KazamaI.etal.(2012)Voltage-dependentbiphasiceffectsofchloroquineondelayedrectifierK(+)-channelcurrentsinmurinethymocytes.JPhysiolSci.PMID22328488
DifferentpotassiumchannelsareinvolvedinrelaxationofratrenalarteryinducedbyP1075
TheATP-sensitiveK(+)channelsopener(K(ATP)CO),P1075[N-cyano-N’-(1,1-dimethylpropyl)-N″-3-pyridylguanidine],hasbeenshowntocauserelaxationofvariousisolatedanimalandhumanbloodvesselsbyopeningofvascularsmoothmuscleATP-sensitiveK(+)(K(ATP))channels.Inadditiontothewell-knowneffectontheopeningofK(ATP)channels,ithasbeenreportedthatvasorelaxationinducedbysomeoftheK(ATP)COsincludessomeotherK(+)channelsubtypes.GiventhatthereisstillnoinformationonothertypesofK(+)channelspossiblyinvolvedinthemechanismofrelaxationinducedbyP1075,thisstudywasdesignedtoexaminetheeffectsofP1075ontheratrenalarterywithendotheliumandwithdenudedendotheliumandtodefinethecontributionofdifferentK(+)channelsubtypesintheP1075actiononthisbloodvessel.OurresultsshowthatP1075inducedaconcentration-dependentrelaxationofratrenalarteryringspre-contractedbyphenylephrine.Glibenclamide,aselectiveK(ATP)channelsinhibitor,partlyantagonizedtherelaxationofratrenalarteryinducedbyP1075.Tetraethylammonium(TEA),anon-selectiveinhibitorofCa(2+)-activatedK(+)channels,aswellasiberiotoxin,amostselectiveblockeroflarge-conductanceCa(2+)-activatedK(+)(BK(Ca))channels,didnotabolishtheeffectofP1075onratrenalartery.Incontrast,anon-selectiveblockerofvoltage-gatedK(+)(K(V))channels,4-aminopyridine(4-AP),aswellasmargatoxin,apotentinhibitorofK(V)1.3channels,causedpartialinhibitionoftheP1075-inducedrelaxationofratrenalartery.Inaddition,inthisstudy,P1075relaxedcontractionsinducedby20mMK(+),buthadnoeffectoncontractionsinducedby80mMK(+).OurresultsshowedthatP1075inducedstrongendothelium-independentrelaxationofratrenalartery.ItseemsthatK(ATP),4-AP-andmargatoxin-sensitiveK(+)channelslocatedinvascularsmoothmusclemediatedtherelaxationofratrenalarteryinducedbyP1075.
NovakovicA.,etal.(2012)DifferentpotassiumchannelsareinvolvedinrelaxationofratrenalarteryinducedbyP1075.BasicClinPharmacolToxicol.PMID22225832
Chemicalsynthesisandstructure-functionstudiesofmargatoxin,apotentinhibitorofvoltage-dependentpotassiumchannelinhumanTlymphocytes
The39aminoacidpeptide,margatoxin(MgTX),apotentinhibitorofthevoltage-activatedpotassiumchannel(Kv1.3)inhumanTlymphocytes,wassynthesizedbyasolidphasetechnique.FormationofthedisulfidebridgeswasrapidatpH8.2.Thefinalproductwaspurifiedtohomogeneityandwasphysicallyandbiologicallyindistinguishablefromthetoxinpreparedbiosynthetically.Thedisulfidebridgepairingwassimilartothatfoundpreviouslyfortherelatedtoxin-charybdotoxin(3):fromCys7toCys29,fromtestedforinhibitionof125Imargatoxinbindingtovoltage-activatedpotassiumchannels.TheresultsindicatethatthethreeC-terminalresiduesofMgTXareimportantfortheefficienttoxinbindingtoKv1.3.
Bednarek,M.A.,etal.(1994)Chemicalsynthesisandstructure-functionstudiesofmargatoxin,apotentinhibitorofvoltage-dependentpotassiumchannelinhumanTlymphocytes,BiochemBiophysResCommun.PMID: 8297371
Determinationofthethree-dimensionalstructureofmargatoxinby1H,13C,15Ntriple-resonancenuclearmagneticresonancespectroscopy
Thesolution structure ofthe39-residuepeptide margatoxin,ascorpiontoxinthatselectivelyblocksthevoltage-gatedpotassium-channelKv1.3,hasbeendeterminedbyNMR spectroscopy.Thetoxinwasisotopicallylabeledwith 13C and 15N andstudiedusingtwo-dimensionalhomonuclearandthree-andfour-dimensionalheteronuclearNMR spectroscopy.Thefinal structure wasdeterminedusing501constraints,comprising422NOEconstraints,60dihedralangleconstraints,9disulfideconstraints,and10hydrogenbondconstraints.StructureswereinitiallydeterminedwiththeprogramPEGASUSandsubsequentlyrefinedwithX-PLOR.Theaveragermsdeviationfromacalculatedaverage structure forthebackboneatomsofresidues3-38is0.40A.Ahelixispresentfromresidues11to20andincludestwoprolineresiduesatpositions15and16.Aloopatresidues21-24leadsintoatwo-strandantiparallelsheetfromresidues25to38withaturnatresidues30-33.Residues3-6runadjacenttothe33-38strandbutdonotformacanonicalbeta-strand.Thetwoadditionalresiduesof margatoxin,relativetotherelatedtoxinscharybdotoxinandiberiotoxin,insertinamannerthatextendsthebeta-sheetbyoneresidue.Otherwise,theglobal structure isverysimilartothatofthesetwoothertoxins.Thelongersheetmayhaveimplicationsforchannelselectivity.
Johnson,B.A.,etal.(1994)Determinationofthethree-dimensionalstructureofmargatoxinby1H,13C,15Ntriple-resonancenuclearmagneticresonancespectroscopy,Biochemistry.PMID: 7999764
Purification,characterization,andbiosynthesisofmargatoxin,acomponentofCentruroidesmargaritatusvenomthatselectivelyinhibitsvoltage-dependentpotassiumchannels
AnovelpeptidylinhibitorofK+channelshasbeenpurifiedtohomogeneityfromvenomofthenewworldscorpionCentruroidesmargaritatus.Theprimarystructureofthis39-amino-acidpeptide,whichwetermmargatoxin(MgTX),wasdeterminedbyaminoacidcompositionalanalysisandpeptidesequencing.MargatoxinpotentlyinhibitsbindingofrADIolabeledcharybdotoxin(ChTX)tovoltage-activatedchannelsinbrainsynapticplasmamembranes.LikeChTX,MgTXblocksthen-typecurrentofhumanT-lymphocytes(Kv1.3channel),butcomparedtoChTX,is20-foldmorepotent(half-blockatapproximately50pM),hasaslowerdissociationrate,andhasnoeffectoncalcium-activatedchannels.Todemonstratethatthesecharacteristicsareduesolelytothepurifiedtoxin,recombinantMgTXwasexpressedinEscherichiacoliaspartofafusionprotein.Aftercleavageandfolding,purifiedrecombinantMgTXdisplayedthesamepropertiesasnativepeptide.ReplacementoftheCOOH-terminalhistidineresidueofMgTXwithasparagineresultedinapeptidewitha10-foldreductioninpotency.Thiswasduetoafasterapparentdissociationrate,suggestingthattheCOOH-terminalaminoacidmayplayanimportantroleinthebindingofMgTXtotheKv1.3channel.MgTXdisplayssignificantsequencehomologywithpreviouslyidentifiedK+channelinhibitors(e.g.ChTX,iberiotoxin,noxiustoxin,andkaliotoxin).However,givenitspotencyanduniqueselectivity,MgTXrepresentsanespeciallyusefultoolwithwhichtostudythephysiologicroleofKv1.3channels.
Garcia-Calvo,etal.(1993)Purification,characterization,andbiosynthesisofmargatoxin,acomponentofCentruroidesmargaritatusvenomthatselectivelyinhibitsvoltage-dependentpotassiumchannels,JBiolChem. PMID: 8360176
Smartox Biotechnolgy的多肽毒素产品如下：
1. 作用于钠离子通道(Sodium channel)的毒素
Toxin name | Catalog # | Target |
Phrixotoxin-3 | 13PHX003 | Selective blocker of Nav1.2 |
µ-conotoxin GIIIB | CON020 | Selective blocker of Nav1.4 |
µ-conotoxin CnIIIC | CON021 | Selective blocker of Nav1.4 |
μ-conotoxin PIIIA | 08CON006 | Selective blocker of Nav1.4 |
Jingzhaotoxin-III | 12JZH003 | Selective blocker of Nav1.5 |
ProTx-II | 07PTX002 | Selective blocker of Nav1.7 |
ProTx-II Biotin | 12PTB002 | Selective blocker of Nav1.7 |
ProTx-I | 12PTX001 | Blocker of Nav1.8, Nav1.2, Nav1.5, Nav1.7 |
Huwentoxin-I | 07HWT001 | Blocker of TTX-S |
Huwentoxin-IV | 08HWT002 | Blocker of TTX-S |
Hainantoxin-III | 13HTX003 | Blocker of TTX-S |
Hainantoxin-IV | 12HTX001 | Blocker of TTX-S |
GsAF-I | 12GSF001 | Blocker of TTX-S |
GsAF-II | 12GSF002 | Blocker of TTX-S |
2. 作用于钾离子通道(Potassium channel)的毒素
Toxin name | Catalog # | Target |
KCa channels | ||
Apamin 蜜蜂神经毒素 | 08APA001 | SK1, SK2, SK3 |
Charybdotoxin 蝎毒素 | 11CHA001 | KCa1.1, KCa3.1 - Kv1.2, Kv1.3, Kv1.6 |
Iberiotoxin | 12IBX001 | KCa1.1 |
Leiurotoxin 1 (Scyllatoxin) | 10LEI001 | SK1, SK2, SK3 |
Tamapin | 10TAM001 | SK1, SK2, SK3 |
Kaliotoxin-1 | 08KTX002 | BK, Kv1.1, Kv1.2, Kv1.3 |
Kv channels | ||
ShK | 08SHK001 | Kv1.3, Kv1.1, Kv1.4, Kv1.6 |
TMR-ShK | SAT001 | Kv1.3, Kv1.1 |
Margatoxin | 08MAG001 | Kv1.3 |
(Dap22)-ShK | 13SHD001 | Kv1.3 |
ADWX-1 | 13ADW001 | Kv1.3 |
HsTx1 | 08NEU001 | Kv1.3, Kv1.2 |
Agitoxin-2 | 13AGI002 | Kv1.3, Kv1.1 |
Maurotoxin | 08MAR001 | Kv1.2, KCa3.1 |
Guangxitoxin 1E | 11GUA002 | Kv2.1, Kv2.2 |
Stromatoxin 1 NEW | SCT01 | Kv2.1, Kv2.2 |
Kaliotoxin-1 | 08KTX002 | BK, Kv1.1, Kv1.2, Kv1.3 |
Charybdotoxin | 11CHA001 | KCa1.1, KCa3.1 - Kv1.2, Kv1.3, Kv1.6 |
Phrixotoxin-2 | PHX002 | Kv4.2, Kv4.3 |
AmmTx3 NEW | AMX001 | A-type potassium channels |
Inwardly rectifying potassium channels | ||
TertiapinQ | 08TER001 | Kir1.1, Kir3.1/3.4, Kir3.1/3.2-KCa1.1 |
hERG/Kv11.1 | ||
BeKm-1 | 13BEK001 | ERG1 |
3. 作用于钙离子通道(Calcium channel)的毒素
Toxin name | Catalog # | Target |
High voltage-gated Ca2+ channels | ||
ω-agatoxin IVA | 11AGA001 | P/Qtype |
ω-Conotoxin MVIIC | 08CON002 | P/Qtype, N-type |
ω-Conotoxin MVIIA | 08CON001 | N-type |
ω-Conotoxin GVIA | 08CON003 | N-type |
ω-Conotoxin SO3 | 08CON013 | N-type |
Huwentoxin I | 07HWT001 | N-type |
ProTx-II | 07PTX002 | T-type, L-type |
Intermediate voltage-gated Ca2+ channels | ||
SNX482 | 08SNX002 | R-type |
Low voltage-gated Ca2+ channels | ||
ProTx-I | 12PTX001 | T-type |
ProTx-II | 07PTX002 | T-type, L-type |
Ryanodine receptors | ||
Maurocalcine | 07PAU001 | Ryr1 |
4. 作用于氯离子通道(Chloride channel)的毒素
Toxin name | Catalog # | Target |
Chlorotoxin | 08CHL001 | Blocker of small conductance Cl- channels |
GaTx1 | 13GTX001 | Selective blocker of CFTR channel |
GaTx2 | 10GTX002 | Selective blocker of ClC-2 channel |
5. 作用于乙酰胆碱受体(Acetylcholine receptor)的毒素
Toxin name | Catalog # | Target |
α-conotoxin PeIA | 13CON017 | α9α10, α3β2 subunits |
α-Conotoxin PrXA | 13CON016 | α1/β1/ε/δ, α1/β1/γ/δ subunits |
Waglerin-1 | 12WAG001 | MusclenAChR |
α-conotoxin MI | 08CON012 | α1/δsubunits |
α-conotoxin GI | 08CON005 | α/δsite |
α-conotoxin IMI | 08CON011 | α7 homomeric nAChR |
α-conotoxin GID | CON019 | Blocker of α3β2, α7 and α4β2 nAChRs |
6. 含N-甲基-D-天冬氨酸NR2B
(NMDA, NR2B containing N-methyl-D-aspartate)
Conantokin-G
选择性、特异性抑制含NR2B的NMDAR。Conantokin-G能剂量依赖性抑制Ca2+内流，抑制NMDA诱导的兴奋性中毒效应。研究表明，在小鼠皮层神经元，Conantokin-G阻滞NMDA引发的电流信号的IC50值为480 nM。
7. 作用于酸敏感离子通道(ASIC channel, Acid-Sensing Ion Channel)的毒素
Toxin name | Catalog # | Target |
APETx2 | 07APE002 | Selective blocker of ASIC3 |
Psalmotoxin1/PcTx1 | 13PCT001 | Selective blocker of ASIC1a |
Ugr9-1 | 13UGR001 | Blocker of ASIC3 |
8. 作用于瞬时受体电位(TRP channel, transient receptor potential)的毒素
Toxin name | Catalog # | Target |
GsMTx4 | 08GSM001 | TRPC, TRPA |
Vanillotoxin3 | 10VAN003 | Activator of TRPV1 |
ProTx-I | 12PTX001 | Antagonist of TRPA1 |
9. 作用于嘌呤能通道(Purinergic channel)的毒素
Purotoxin-1
选择性抑制P2X3受体。100 nM Purotoxin-1 (PT-1)选择性抑制P2X3受体通道，在大鼠DRG神经元上，使用膜片钳实验表明：PT-1对电压门控通道和TRPV1均无抑制效应。10 µM ATP和100 µM α,β Methylene-ATP浓度下Purotoxin-1对P2X3受体有选择性作用，在该ATP浓度下Purotoxin-1对P2X2和杂化二聚体P2X2/3并无激动作用。Purotoxin-1对疼痛的潜在治疗作用。
10. 作用于其它膜受体通道(Others)的毒素
Smartox Biotechnology还提供其他类型的膜受体抑制剂：
Toxin name | Catalog # | Target |
Morphiceptin | 011CAS001 | Agonist of µ-opoid receptors |
Lys-conopressin G | 11CON14 | Vasopressin-like peptide |
GsMTx4 | 08GSM001 | Mechano sensitive ion channels |
Obtustatin | 10OBT001 | Blocks the binding of α1β1 integrin to collagen IV |
Rho-Conotoxin TIA | CON022 | Blocks α1-adrenergic receptor |
公司简介
Smartox Biotechnology是全球唯一一家专门生产动物毒液多肽毒素，用于细胞离子通道功能研究的生物医药公司。多肽毒素在生物制药领域具有重要的使用价值。
Smartox Biotechnology于2009年由来自Grenoble神经科学研究所(Grenoble Institute of Neuroscience)的Michel De Waard博士创立。Smartox Biotechnology专门研究动物毒液，制作合成多种毒液中的多肽成分（常称为毒素）。De Waard博士研究离子通道与毒素多肽的关系，尤其是鉴定、开发毒素多肽作为治疗性分子或细胞穿透肽(cell penetrating peptides, CPP)。其研究团队在毒液分离，药理性活性肽鉴定、富半胱氨酸肽定性、制作和优化等方面具有独特、丰富的经验。2010年，Smartox Biotechnolgy被法国研究部(Ministry of Research)授予“新兴企业OSEO奖(OSEO prize for emerging businesses)”。
总之，Smartox Biotechnolgy提供一系列高质量、具开创价值的多肽毒素。这些化合物在离子通道 研究中具有高的亲和性和选择性，是相应领域科学研究理想的生物毒素提供商和贴心的合作伙伴。
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