ShK(StichodactylahelianthusNeurotoxin)hasbeenisolatedfromthevenomoftheCarribeanseaanemoneStoichactishelianthus.ShKinhibitsvoltage-dependentpotassiumchannels.ItblocksKv1.3(KCNA3)potentlyandalsoKv1.1(KCNA1),Kv1.4(KCNA4)andKv1.6(KCNA6)respectivelywithaKdof11pM,16pM,312pMand165pM.Interestingly,itwasalsodemonstratedthatShKpotentlyinhibitsthehKv3.2bchannelwithanIC50valueofapproximately0.6nM.
Description:
AAsequence:Arg-Ser-Cys3-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys12-Thr-Ala-Phe-Gln-Cys17-Lys-His-Ser-Met-Lys-Tyr-Arg-Leu-Ser-Phe-Cys28-Arg-Lys-Thr-Cys32-Gly-Thr-Cys35-OH
Disulfidebonds:Cys3-Cys35,Cys12-Cys28andCys17-Cys32
Length(aa):35
Formula:C169H274N54O48S7
MolecularWeight:4054.85Da
Appearance:Whitelyophilizedsolid
Solubility:waterandsalinebuffer
CASnumber:165168-50-3
Source:Synthetic
Purityrate:>97%
Reference:
DurablepharmacologicalresponsesfromthepeptideShK-186,aspecificKv1.3channelinhibitorthatsuppressesTcellmediatorsofautoimmunedisease
TheKv1.3channelisarecognizedtargetforpharmaceuticaldevelopmenttotreatautoimmunediseasesandorganrejection.ShK-186,aspecificpeptideinhibitorofKv1.3,hasshownpromiseinanimalmodelsofmultiplesclerosisandrheumatoidarthritis.Here,wedescribethepharmacokinetic-pharmacodynamicrelationshipforShK-186inratsandmonkeys.ThepharmacokineticprofileofShK-186wasevaluatedwithavalidatedhigh-performanceliquidchromatography-tandemmassspectrometrymethodtomeasurethepeptide’sconcentrationinplasma.Theseresultswerecomparedwithsingle-photonemissioncomputedtomography/computedtomographydatacollectedwithan¹¹¹In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid-conjugateofShK-186toassesswhole-bloodpharmacokineticparametersaswellasthepeptide’sabsorption,distribution,andexcretion.AnalysisofthesedatasupportamodelwhereinShK-186isabsorbedslowlyfromtheinjectionsite,resultinginbloodconcentrationsabovetheKv1.3channel-blockingIC₅₀valueforupto7daysinmonkeys.PharmacodynamicstudiesonhumanperipheralbloodmononuclearcellsshowedthatbriefexposuretoShK-186resultedinsustainedsuppressionofcytokineresponsesandmaycontributetoprolongeddrugeffects.Indelayed-typehypersensitivity,chronicrelapsing-remittingexperimentalautoimmuneencephalomyelitis,andpristane-inducedarthritisratmodels,asingledoseofShK-186every2to5dayswasaseffectiveasdailyadmiNISTration.ShK-186’sslowdistributionfromtheinjectionsiteanditslongresidencetimeontheKv1.3channelcontributetotheprolongedtherapeuticeffectofShK-186inanimalmodelsofautoimmunedisease.
TarchaEJ.,etal.(2012)DurablepharmacologicalresponsesfromthepeptideShK-186,aspecificKv1.3channelinhibitorthatsuppressesTcellmediatorsofautoimmunedisease.JPharmacolExpTher.PMID: 22637724
ThebeneficialeffectofblockingKv1.3inthepsoriasiformSCIDmousemodel
TheKv1.3channelisimportantintheactivationandfunctionofeffectormemoryTcells.Recently,specificblockersoftheKv1.3channelhavebeendevelopedasapotentialtherapeuticoptionfordiverseautoimmunediseases.Inpsoriaticlesions,mostlymphocytesarememoryeffectorTcells.TheaimofthepresentstudywastodetecttheexpressionofKv1.3channelsinthesecellsinpsoriaticlesionsaswellasinhumanpsoriasiformskingraftsusingtheseverecombinedimmunodeficient(SCID)mousemodel.HistologicalandimmunohistochemicalstainingforKv1.3expressionandvariousinflammatoryMarkerswasperformedinsectionsobtainedfromsixpsoriaticpatientsand18beige-SCIDmicewithpsoriasiformhumanskingrafts.SixgraftedmiceweretreatedwithStichodactylahelianthusneurotoxin(ShK),aknownKv1.3blocker.TheresultsshowedanincreasednumberofKv1.3+cellsinthepsoriaticskinaswellasinthepsoriasiformskingraftsascomparedwithnormalskinandnormalskingrafts.InjectionsofShKshowedamarkedtherapeuticeffectinthreeofsixpsoriasiformskingrafts.AsignificantlydecreasednumberofKv1.3+cellswasobservedintheresponderscomparedwiththecontrolgrafts.Thispilotstudy,althoughperformedinasmallnumberofmice,revealsthepossIBLebeneficialeffectofKv1.3blockersinpsoriasispatients.
GilharA.,etal.(2011)ThebeneficialeffectofblockingKv1.3inthepsoriasiformSCIDmousemodel.JInvestDermatol.PMID: 20739949
Modelingthebindingofthreetoxinstothevoltage-gatedpotassiumchannel(Kv1.3)
Theconductionpropertiesofthevoltage-gatedpotassiumchannelKv1.3anditsmodesofinteractionwithseveralpolypeptidevenomsareexaminedusingBrowniandynamicssimulationsandmoleculardynamicscalculations.Employinganopen-statehomologymodelofKv1.3,wefirstdeterminecurrent-voltageandcurrent-concentrationcurvesandascertainthatsimulatedresultsaccordwithexperimentalmeasurements.Wetheninvestigate,usingamoleculardockingmethodandmoleculardynamicssimulations,thecomplexesformedbetweentheKv1.3channelandseveralKv-specificpolypeptidetoxinsthatareknowntointerferewiththeconductingmechanismsofseveralclassesofvoltage-gatedK(+)channels.ThedepthsofpotentialofmeanforceencounteredbycharyBDotoxin,α-KTx3.7(alsoknownasOSK1)andShKare,respectively,-19,-27,and-25kT.Thedissociationconstantscalculatedfromtheprofilesofpotentialofmeanforcecorrespondcloselytotheexperimentallydeterminedvalues.Wepinpointtheresiduesinthetoxinsandthechannelthatarecriticalfortheformationofthestablevenom-channelcomplexes.
ChenR.,etal.(2011)Modelingthebindingofthreetoxinstothevoltage-gatedpotassiumchannel(Kv1.3).BiophysJ.PMID: 22261053
BlockadeofT-lymphocyteKCa3.1andKv1.3channelsasnovelimmunosuppressionstrategytopreventkidneyallograftrejection
Currently,thereisanunmetclinicalneedfornovelimmunosuppressiveagentsforlong-termpreventionofkidneytransplantrejectionasalternativestothenephrotoxiccalcineurininhibitorcyclosporine(CsA).RecentstudieshaveshownthatK(+)channelshaveacrucialroleinT-lymphocyteactivity.WeinvestigatedwhethercombinedblockadeoftheT-cellK(+)channelsK(Ca)3.1andK(v)1.3,bothofwhichregulatecalciumsignalingduringlymphocyteactivation,iseffectiveinpreventionofrejectionofkidneyallograftsfromFisherratstoLewisrats.AllrecipientswereinitiallytreatedwithCsA(5mg/kgd)for7days.Inratswithintactallograftfunction,treatmentwascontinuedfor10dayswitheitherCsA(5mg/kgd),oracombinationofTRAM-34(K(Ca)3.1inhibitor;120mg/kgd)plusStichodactylahelianthustoxin(ShK,K(v)1.3inhibitor;80microg/kg3timesdaily),orvehiclealone.Kidneysectionswerestainedwithperiodicacid-Schifforhematoxylin-eosinandhistochemicallyformarkersofmacrophages(CD68),T-lymphocytes(CD43),orcytotoxicT-cells(CD8).OurresultsshowedthattreatmentwithTRAM-34andShKreducedtotalinterstitialmononuclearcellinfiltration(-42%)andthenumberofCD43+T-cells(-32%),cytotoxicCD8+T-cells(-32%),andCD68+macrophages(-26%)inallograftswhencomparedtovehicletreatmentalone.EfficacyofTRAM-34/ShKtreatmentwascomparablewiththatofCsA.Inaddition,novisibleorgandamageorotherdiscernibleadverseeffectswereobservedwiththistreatment.Thus,selectiveblockadeofT-lymphocyteK(Ca)3.1andK(v)1.3channelsmayrepresentanovelalternativetherapyforpreventionofkidneyallograftrejection.
GrgicI.,etal.(2009)BlockadeofT-lymphocyteKCa3.1andKv1.3channelsasnovelimmunosuppressionstrategytopreventkidneyallograftrejection.TransplantProc.PMID: 19715983
MolecularmechanismoftheseaanemonetoxinShKrecognizingtheKv1.3channelexploredbydockingandmoleculardynamicsimulations
ComputationalmethodsareemployedtosimulatetheinteractionoftheseaanemonetoxinShKincomplexwiththevoltage-gatedpotassiumchannelKv1.3frommice.Alloftheavailable20structuresofShKintheProteinDataBankwereconsideredforimprovingtheperformanceoftherigidproteindockingofZDOCK.ThetrADItionalandnovelbindingmodeswereobtainedamongalargenumberofpredictedcomplexesbyusingclusteringanalysis,screeningwithexpertknowledge,energyminimization,andmoleculardynamicsimulations.Thequalityandvalidityoftheresultingcomplexeswerefurtherevaluatedtoidentifyafavorablecomplexstructureby500psmoleculardynamicsimulationsandthechangeofbindingfreeenergieswithacomputationalalaninescanningtechnique.ThenovelandreasonableShK-Kv1.3complexstructurewasfoundtobedifferentfromthetraditionalmodelbyusingtheLys22residuetoblockthechannelpore.FromtheresultingstructureoftheShK-Kv1.3complex,ShKmainlyassociatesthechanneloutervestibulewithitssecondhelicalsegment.StructuralanalysisfirstrevealedthattheLys22residuesidechainoftheShKpeptidejusthangsbetweenCandDchainsoftheKv1.3channelinsteadofphysicallyblockingthechannelpore.TheobviouslossoftheShKSer20AlaandTyr23AlamutantbindingABIlitytotheKv1.3channeliscausedbytheconformationalchange.ThefivehydrogenbondsbetweenArg24inShKandH404(A)andD402(D)inKv1.3makeArg24themostcrucialforitsbindingtotheKv1.3channel.BesidesthedetailedinteractionbetweenShKandKv1.3attheatomlevel,thesignificantconformationalchangeinducedbytheinteractionbetweentheShKpeptideandtheKv1.3channel,accompaniedbythegradualdecreaseofbindingfreeenergies,stronglyimpliesthatthebindingoftheShKpeptidetowardtheKv1.3channelisadynamicprocessofconformationalrearrangementandenergystabilization.AllofthesecanacceleratethedevelopmentofShKstructure-basedimmunosuppressants.
JinL,WuY.(2007)MolecularmechanismoftheseaanemonetoxinShKrecognizingtheKv1.3channelexploredbydockingandmoleculardynamicsimulations.JChemInfModel. PMID: 17718553
K+channelblockers:noveltoolstoinhibitTcellactivationleadingtospecificimmunosuppression
DuringthelasttwodecadessincetheidentificationandcharacterizationofTcellpotassiumchannelsgreatadvanceshavebeenmadeintheunderstandingoftheroleofthesechannelsinTcellfunctions,especiallyinantigen-inducedactivation.TheirlimitedtissuedistributionandtherecentdiscoverythatdifferentTcellsubtypescarryingoutdistinctimmunefunctionsshowspecificexpressionlevelsofthesechannelshavemadeTcellpotassiumchannelsattractivetargetsforimmunomodulatorydrugs.Manytoxinsofvariousanimalspeciesandastructurallydiversearrayofsmallmoleculesinhibitingthesechannelswithvaryingaffinityandselectivitywerefoundandtheirsuccessfuluseinimmunosuppressioninvivowasalsodemonstrated.Betterunderstandingofthetopologicaldifferencesbetweenpotassiumchannelpores,detailedknowledgeoftoxinandsmall-moleculestructuresandtheidentificationofthebindingsitesofblockingcompoundsmakeitpossibletoimprovetheselectivityandaffinityoftheleadcompoundsbyintroducingmodificationsbasedonstructuralinformation.Inthisreviewthebasicpropertiesandphysiologicalrolesofthevoltage-gatedKv1.3andtheCa2+-activatedIKCa1potassiumchannelsarediscussedalongwithanoverviewofcompoundsinhibitingthesechannelsandapproachesaimingatproducingmoreefficientmodulatorsofimmunefunctionsforthetreatmentofdiseaseslikesclerosismultiplexandtypeIdiabetes.
PanyiG,etal.(2006)K+channelblockers:noveltoolstoinhibitTcellactivationleadingtospecificimmunosuppression.CurrPharmDes. PMID: 16787250
Stichodactylahelianthuspeptide,apharmacologicaltoolforstudyingKv3.2channels
Voltage-gatedpotassium(Kv)channelsregulatemanyphysiologicalfunctionsandrepresentimportanttherapeutictargetsinthetreatmentofseveralclinicaldisorders.Althoughsomeofthesechannelshavebeenwell-characterized,thestudyofothers,suchasKv3channels,hasbeenhinderedbecauseoflimitedpharmacologicaltools.ThecurrentstudywasinitiatedtoidentifypotentblockersoftheKv3.2channel.Chinesehamsterovary(CHO)-K1cellsstablyexpressinghumanKv3.2b(CHO-K1.hKv3.2b)wereestablishedandcharacterized.Stichodactylahelianthuspeptide(ShK),isolatedfromS.helianthusvenomandaknownhigh-affinityblockerofKv1.1andKv1.3channels,wasfoundtopotentlyinhibit86Rb+effluxfromCHO-K1.hKv3.2b(IC50approximately0.6nM).InelectrophysiologicalrecordingsofKv3.2bchannelsexpressedinXenopuslaevisoocytesorinplanarpatch-clampstudies,ShKinhibitedhKv3.2bchannelswithIC50valuesofapproximately0.3and6nM,respectively.DespitethepresenceofKv3.2proteininhumanpancreaticbetacells,ShKhasnoeffectontheKvcurrentofthesecells,suggestingthatitisunlikelythathomotetramericKv3.2channelscontributesignificantlytothedelayedrectifiercurrentofinsulin-secretingcells.InmousecorticalGABAergicfast-spikinginterneurons,however,applicationofShKproducedeffectsconsistentwiththeblockadeofKv3channels(i.e.,anincreaseinactionpotentialhalf-width,adecreaseintheamplitudeoftheactionpotentialafterhyperpolarization,andadecreaseinmaximalfiringfrequencyinresponsetodepolarizingcurrentinjections).Takentogether,theseresultsindicatethatShKisapotentinhibitorofKv3.2channelsandmayserveasausefulpharmacologicalprobeforstudyingthesechannelsinnativepreparations.
YanL.,etal.(2005)Stichodactylahelianthuspeptide,apharmacologicaltoolforstudyingKv3.2channels.MolPharmacol.PMID: 15709110
TargetingeffectormemoryTcellswithaselectivepeptideinhibitorofKv1.3channelsfortherapyofautoimmunediseases
Thevoltage-gatedKv1.3K(+)channelisanoveltargetforimmunomodulationofautoreactiveeffectormemoryT(T(EM))cellsthatplayamajorroleinthepathogenesisofautoimmunediseases.WedescribethecharacterizationofthenovelpeptideShK(L5)thatcontainsl-phosphotyrosinelinkedviaanine-atomhydrophiliclinkertotheNterminusoftheShKpeptidefromtheseaanemoneStichodactylahelianthus.ShK(L5)isahighlyspecificKv1.3blockerthatexhibits100-foldselectivityforKv1.3(K(d)=69pM)overKv1.1andgreaterthan250-foldselectivityoverallotherchannelstested.ShK(L5)suppressestheproliferationofhumanandratT(EM)cellsandinhibitsinterleukin-2productionatpicomolarconcentrations.NaiveandcentralmemoryhumanTcellsareinitially60-foldlesssensitivethanT(EM)cellstoShK(L5)andthenbecomeresistanttothepeptideduringactivationbyup-regulatingthecalcium-activatedK(Ca)3.1channel.ShK(L5)doesnotexhibitinvitrocytotoxicityonmammaliancelllinesandisnegativeintheAmestest.Itisstableinplasmaandwhenadministeredoncedailybysubcutaneousinjection(10mug/kg)attains“steadystate”bloodlevelsofapproximately300pM.ThisregimendoesnotcausecardiactoxicityassessedbycontinuousEKGmonitoringanddoesnotalterclinicalchemistryandhematologicalparametersafter2-weektherapy.ShK(L5)preventsandtreatsexperimentalautoimmuneencephalomyelitisandsuppressesdelayedtypehypersensitivityinrats.ShK(L5)mightproveusefulfortherapyofautoimmunedisorders.
BeetonC.,etal.(2005)TargetingeffectormemoryTcellswithaselectivepeptideinhibitorofKv1.3channelsfortherapyofautoimmunediseases.MolPharmacol. PMID: 15665253
PotassiumchannelblockadebytheseaanemonetoxinShKforthetreatmentofmultiplesclerosisandotherautoimmunediseases
Expressionofthetwolymphocytepotassiumchannels,thevoltage-gatedchannelKv1.3andthecalciumactivatedchannelIKCa1,changesduringdifferentiationofhumanTcells.WhileIKCa1isthefunctionallydominantchannelinnaiveand“early”memoryTcells,Kv1.3iscrucialfortheactivationofterminallydifferentiatedeffectormemory(TEM)Tcells.BecauseoftheinvolvementofTEMcellsinautoimmuneprocesses,Kv1.3isregardedasapromisingtargetforthetreatmentofT-cellmediatedautoimmunediseasessuchasmultiplesclerosisandthepreventionofchronictransplantrejection.ShK,a35-residuepolypeptidetoxinfromtheseaanemone,Stichodactylahelianthus,blocksKv1.3atlowpicomolarconcentrations.ShKadoptsacentralhelix-kink-helixfold,andalanine-scanningandothermutagenesisstudieshavedefineditschannel-bindingsurface.ModelshavebeendevelopedofhowthistoxineffectsK+-channelblockadeandhowitsdockingconfigurationmightdifferinShK-Dap22,whichcontainsasinglesidechainsubstitutionthatconfersspecificityforKv1.3blockade.ShK,ShK-Dap22andtheKv1.3blockingscorpiontoxinkaliotoxinhavebeenshowntopreventandtreatexperimentalautoimmuneencephalomyelitisinrats,amodelformultiplesclerosis.AfluoresceinatedanalogofShK,ShK-F6CA,hasbeendeveloped,whichallowsthedetectionofactivatedTEMcellsinhumanandanimalbloodsamplesbyflowcytometryandthevisualizationofKv1.3channeldistributioninlivingcells.ShKanditsanalogsarecurrentlyundergoingfurtherevaluationasleadsinthedevelopmentofnewbiopharmaceuticalsforthetreatmentofmultiplesclerosisandotherT-cellmediatedautoimmunedisorders.
NortonRS.,etal.(2004)PotassiumchannelblockadebytheseaanemonetoxinShKforthetreatmentofmultiplesclerosisandotherautoimmunediseases.CurrMedChem.PMID: 15578998
SolutionstructureofShKtoxin,anovelpotassiumchannelinhibitorfromaseaanemone
AnessentialbindingsurfaceforShKtoxininteractionwithratbrainpotassiumchannels.
An“Alascan”analysisofShKtoxin,a35-residuebasicpeptidepossessingthreedisulfidebonds,identifiessevensidechainswhichinfluencebindingtobraindelayedrectifierpotassiumchannels.Additionalanalogsweresynthesizedandtestedtofurtherdeciphertherolesoftheseresidues,particularlyTyr23.Theinhibitoryeffectsoftheseanalogson125I-labeleddendrotoxinbindingtoratbrainmembranesshowedthatreplacementofTyr23withAladrasticallyloweredtheaffinityofthetoxinfortheKv1.2channels.AlasubstitutionofPhe27reducedpotencymorethan15-fold.MonosubstitutedAlaanalogsforIle7,Ser20,orLys30eachdisplayed5-foldreductionsinpotency.Thus,aromaticityatposition23isimportantforeffectivedelayedrectifierbrainKchannelbinding.Incontrast,thearomaticresidueatposition27wasnotcritical,sincecyclohexylalaninesubstitutionincreasedaffinity.ThesolutionstructureofShKtoxinclustersIle7,Arg11,Ser20,Lys22,Tyr23,andPhe27incloseproximity,formingthepotassiumchannelbindingsurfaceofthetoxin.WeproposeanessentialbindingsurfaceonthetoxininwhichLys22andTyr23aremajorcontributors,throughionicandaromatic(hydrophobic)interactions,withthepotassiumchannel.
PenningtonMW.,etal.(1996)AnessentialbindingsurfaceforShKtoxininteractionwithratbrainpotassiumchannels.Biochemistry. PMID: 8987971
CharacterizationofapotassiumchanneltoxinfromtheCaribbeanSeaanemoneStichodactylahelianthus
Apeptidetoxin,ShK,thatblocksvoltage-dependentpotassiumchannelswasisolatedfromthewholebodyextractoftheCaribbeanseaanemoneStichodactylahelianthus.ItcompeteswithdendrotoxinIandalpha-dendrotoxinforbindingtosynaptosomalmembranesofratbrain,facilitiesacetylcholinereleaseatanavianneuromuscularjunctionandsuppressesK+currentsinratdorsalrootganglionneuronesinculture.ItsaminoacidsequenceisR1SCIDTIPKS10RCTAFQCKHS20MKYRLSFCRK30TCGTC35.ThereisnohomologywithotherK+channel-blockingpeptides,exceptforBgKfromtheseaanemoneBunodosomagranulifera.ShKandBgKappeartobeinadifferentstructuralclassfromothertoxinsaffectingK+channels.
Castaneda,O.,etal.(1995)CharacterizationofapotassiumchanneltoxinfromtheCaribbeanSeaanemoneStichodactylahelianthus,Toxicon. PMID: 7660365
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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