Conantokin-GisaconopeptidethathasbeenisolatedfromthevenomoftheconeConusgeographus. Conantokin-Gselectivelyinhibits NR2B containingN-methyl-D-aspartatereceptors(NMDAR)withahighspecificity.Thus, Conantokin-G inhibitsinaconcentration-dependentmannertheCa2+ influxleADIngtoaneuroprotectiveeffectagainstNMDA-inducedexcitotoxicity. Conantokin-G wasshowntoblockNMDA-evokedcurrentsinmurinecorticalneuronswithanIC50 valueofaround480nM.
Description:
AAsequence: Gly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2
Length(aa): 17
Formula: C88H138N26O44
MolecularWeight: 2264.23Da
Appearance: Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber: [93438-65-4]Source: Synthetic
Purityrate: >95%
Reference:
Opposingactionofconantokin-Gonsynapticallyandextrasynaptically-activatedNMDAreceptors
SynapticandextrasynapticactivationoftheN-methyl-D-aspartatereceptor(NMDAR)hasdistinctconsequencesoncellsignalingandneuronalsurvival.Sinceconantokin(con)-GantagonismisNR2B-selective,whichisthekeysubunitinvolvedinextrasynapticactivationofthereceptor,itsABIlitytospecificallyelicitdistinctsignalingoutcomesinneuronswithsynapticallyorextrasynaptically-activatedNMDARswasevaluated.InhibitionofCa(2+)influxthroughextrasynapticNMDARionchannelswasneuroprotective,asiteffectivelyenhancedlevelsofactivatedextracellularsignal-regulatedkinase1/2(ERK1/2),activatedcAMPresponseelementbindingprotein(CREB),enhancedmitochondrialviability,andattenuatedtheactindisorganizationobservedbyextrasynapticactivationofNMDARs.Conversely,thepro-signalingpathwaysstimulatedbysynaptically-inducedCa(2+)influxwereabolishedbycon-G.FurThermore,subunitnon-selectivecon-Twasunabletosuccessfullyredresstheimpairmentsinneuronscausedbyextrasynaptically-activatedNMDARs,thusindicatingthatNR2B-specificantagoNISTsarebeneficialforneuronsurvival.NeuronsablatedfortheNR2BsubunitshowedweaksynapticCa(2+)influx,reducedsensitivitytoMK-801blockage,anddiminishedextrasynapticcurrentcomparedtoWTandNR2A(-/-)neurons.ThisindicatesthattheNR2BsubunitisanintegralcomponentofbothsynapticandextrasynapticNMDARchannels.Altogether,thesedatasuggestthatcon-GspecificallytargetstheNR2Bsubunitinthesynapticandextrasynapticlocations,resultingintheopposingactionofcon-GondifferentiallyactivatedpoolsofNMDARs.
BalsaraR., etal. (2012)Opposingactionofconantokin-Gonsynapticallyandextrasynaptically-activatedNMDAreceptors.Neuropharmacology. PMID: 22306487
CGX-1007preventsexcitotoxiccelldeathviaactionsatmultipletypesofNMDAreceptors
Glutamateinducedexcitotoxicinjurythroughover-activationofN-methyl-D-aspartatereceptors(NMDARs)playsacriticalroleinthedevelopmentofmanyneurodegenerativediseases.ThepresentstudywasundertakentoevaluatetheroleofCGX-1007(ConantokinG)asaneuroprotectiveagentagainstNMDA-inducedexcitotoxicity.ConantokinG,aconesnailpeptideisolatedfromConusgeographusisreportedtoselectivelyinhibitNR2BcontainingNMDARswithhighspecificityandisshowntohavepotentanticonvulsantandantinociceptiveeffects.CGX-1007significantlyreducedtheexcitotoxiccelldeathinducedbyNMDAinorganotypichippocampalbrainsliceculturesinaconcentration-dependentmanner.Incontrast,ifenprodil,anotherNR2BspecificantagonistfailedtoofferneuroprotectionagainstNMDA-inducedexcitotoxicity.WefurtherdeterminedthattheneuroprotectionobservedislikelyduetotheactionofCGX-1007atmultipleNMDAreceptorsubtypes.Inaseriesofelectrophysiologyexperiments,CGX-1007inhibitedNMDA-gatedcurrentsinhumanembryonickidney(HEK)293cellsexpressingNMDAreceptorscontainingeitherNR1a/NR2BorNR1a/NR2Asubunitcombinations.CGX-1007producedaweakinhibitionatNR1a/NR2Creceptors,whereasithadnoeffectonNR1a/NR2Dreceptors.Further,theinhibitionofNMDAreceptorsbyCGX-1007wasvoltage-dependentwithgreaterinhibitionseenathyperpolarizedmembranepotentials.Thevoltage-dependenceofCGX-1007activitywasalsoobservedinrecordingsofNMDA-gatedcurrentsevokedinnativereceptorsexpressedincorticalneuronsinculture.Basedonourresults,weconcludethatCGX-1007isapotentneuroprotectiveagentthatactsasanantagonistatbothNR2AandNR2Bcontainingreceptors.
AlexAB., etal. (2011)CGX-1007preventsexcitotoxiccelldeathviaactionsatmultipletypesofNMDAreceptors.Neurotoxicology. PMID: 21396956
SpecificdeterminantsofconantokinsthatdictatetheirselectivityfortheNR2BsubunitofN-methyl-D-aspartatereceptors.
Conantokinsarenaturally-occurringsmallpeptideantagonistsofionflowthroughNMDA/glycineactivated-N-methyl-d-aspartatereceptor(NMDAR)ionchannels.Onememberoftheconantokinfamily,conantokin(con)-G,a17-residuepeptide,isselectiveforNMDARscontainingtheN-methyl-d-aspartatereceptorsubunit2B(NR2B),whereasthehomologouspeptides,con-Tandcon-R,showbroaderselectivityforNR2subunits.Inthisstudy,con-G,con-R,andcon-Tvariantswerechemicallysynthesizedandemployedtoinvestigatetheirsubunitselectivitiesasinhibitorsofagonist-evokedioncurrentsinhumanembryonickidney-293(HEK-293)cellsexpressingvariouscombinationsofNMDARsubunitsthatcontainNR1aorNR1bcombinedwithNR2AorNR2B.Usingtruncationandpointmutants,aswellaschimericconantokins,wedeterminedthattheN-terminusofcon-GcontainsallthedeterminantsforNR2Bselectivity.Withthisinformation,alargenumberof(con)variantsweresynthesizedandusedtoestablishminimalsequencedeterminantsforselectivity.Tyratposition5broadenstheNR2selectivity,andrecoveryofNR2BselectivityinTyr5peptideswasachievedbyincorporatingAlaorGlyatposition8.NR2Bselectivityincon-RcanbeconferredthroughdeletionoftheAlaatposition10,therebyshiftingtheγ-carboxyglutamate(Gla)fromposition11toposition10,whereaGlanaturallyoccursincon-Gandcon-T.Thenatureoftheaminoacidatposition6isalsolinkedtosubunitselectivity.OurstudiessuggestthatthemoleculardeterminantsofconantokinsthatdictateNMDARsubunitselectivityarehousedinspecificresiduesoftheN-terminiofthesepeptides.Thus,itispossIBLetoengineerdesiredNMDARfunctionalpropertiesintoconantokin-basedpeptides.
ShengZ., etal. (2010)SpecificdeterminantsofconantokinsthatdictatetheirselectivityfortheNR2BsubunitofN-methyl-D-aspartatereceptors. Neuroscience. PMID: 20688135
Theselectivityofconantokin-GforionchannelinhibitionofNR2Bsubunit-containingNMDAreceptorsisregulatedbyaminoacidresiduesintheS2regionofNR2B
Theconantokinsareshort,naturallyoccurringpeptidesthatinhibitionflowthroughN-methyl-d-aspartatereceptor(NMDAR)channels.Onememberofthispeptidefamily,conantokin-G(con-G),showshighselectivityforantagonismofNR2B-containingNMDARchannels,whereasotherknownconantokinsarelessselectiveinhibitorswithregardtothenatureoftheNR2subunitoftheNMDARcomplex.InordertodefinethemoleculardeterminantsofNR2Bthatgoverncon-Gselectivity,weevaluatedtheabilityofcon-GtoinhibitNMDARionchannelsexpressedinhumanembryonickidney(HEK)293cellstransfectedwithNR1,incombinationwithvariousNR2A/2Bchimerasandpointmutants,byelectrophysiologyusingcellsvoltage-clampedinthewhole-cellconfiguration.Wefoundthatavariantofthecon-G-insensitivesubunit,NR2A,inwhichthe158residuescomprisingtheS2peptidesegment(E(657)-I(814))werereplacedbythecorrespondingS2regionofNR2B(E(658)-I(815)),resultsinreceptorsthatarehighlysensitivetoinhibitionbycon-G.Ofthe22aminoacidsthataredifferentbetweentheNR2A-S2andtheNR2B-S2regions,exchangeofoneofthese,M(739)ofNR2BfortheequivalentK(738)ofNR2A,wassufficienttocompletelyimporttheinhibitoryactivityofcon-GintoNR1b/NR2A-containingNMDARs.Somereinforcementofthiseffectwasfoundbysubstitutionofasecondaminoacid,K(755)ofNR2BforY(754)ofNR2A.ThediscoveryofthemoleculardeterminantsofNR2Bselectivitywithcon-Ghasimplicationsforthedesignofsubunit-selectiveneuroBIOLOGicalprobesanddrugtherapies,inadditiontoadvancingourunderstandingofNR2B-versusNR2A-mediatedneurologicalprocesses.
ShengZ., etal.(2009)Theselectivityofconantokin-GforionchannelinhibitionofNR2Bsubunit-containingNMDAreceptorsisregulatedbyaminoacidresiduesintheS2regionofNR2B. Neuropharmacology. PMID: 19427876
Powerfulantinociceptiveeffectsoftheconesnailvenom-derivedsubtype-selectiveNMDAreceptorantagonistsconantokinsGandT
Subunitnon-selectiveN-methyl-D-aspartate(NMDA)receptorantagonistsreduceinjury-inducedpainbehavior,butgenerallyproduceunacceptablesideeffects.Inthisstudy,weexaminedtheantinociceptiveandmotoreffectsofconesnailvenom-derivedpeptides,conantokinsGandT(conGandconT),whichareselectiveinhibitorsoftheNR2BorNR2AandNR2BsubtypesoftheNMDAreceptor,respectively.WetestedtheeffectsofconGandconTinmodelsoftissue(formalintest),nerveinjury(partialsciaticnerveligation)andinflammation-induced(intraplantarCompleteFreund’sAdjuvant;CFA)paininmice.Intheformalintest,intrathecal(i.t.)conGorconTsuppressedtheongoingpainbehavior(ED(50)and95%confidenceintervals(CI),11(7-19)and19(11-33),respectively)atdosesthatwere17-27timeslowerthanthoserequiredtoimpairmotorfunction(acceleratingrotarodtreadmilltest:ED(50)and95%CI,300(120-730)and320(190-540)pmol,respectively).Bycomparison,SNX-111,anN-typevoltage-sensitivecalciumchannelantagonistthatisalsoderivedfromconesnailvenom,producedsignificantmotorimpairmentatadose(3.0pmol,i.t.)thatwasonlypartiallyefficaciousintheformalintest.Furthermore,conGreversedtheallodyniaproducedbynerveinjury,withgreaterpotencyonthermal(ED50and95%CI,24(10-55)pmol)thanonmechanicalallodynia(59(33-105)pmol).Finally,asingledoseofconG(100pmol,i.t.)alsoreducedCFA-evokedthermalandmechanicalallodynia.Takentogether,theseresultsdemonstratethatconantokinsexhibitpotentantinociceptiveeffectsinseveralmodelsofinjury-inducedpain.ThestudysupportsthenotionthatdrugsdirectedagainstsubtypesoftheNMDAreceptor,byvirtueoftheirreducedside-effectprofile,holdpromiseasnoveltherapeuticagentsforthecontrolofpain.
Malmberg,AB., etal.(2003)Powerfulantinociceptiveeffectsoftheconesnailvenom-derivedsubtype-selectiveNMDAreceptorantagonistsconantokinsGandT, Pain. PMID: 12507705
Theaminoacidresidueatsequenceposition5intheconantokinpeptidespartiallygovernssubunit-selectiveantagonismofrecombinantN-methyl-D-aspartatereceptors
Wholecellvoltageclamprecordingswereperformedtoassesstheabilityof conantokin-G(con-G), conantokin-T(con-T),anda17-residue truncatedformof conantokin-R(con-R[1-17])toinhibit N-methyl-d-aspartate (NMDA)-evokedcurrentsinhumanembryonickidney293cellstransientlyexpressingvariouscombinationsofNR1a,NR1b,NR2A,andNR2Breceptorsubunits.Con-Tandcon-R[1-17]attenuatedioncurrentsincellsexpressingNR1a/NR2AorNR1a/NR2B.Con-GdidnotaffectNMDA-evokedioniccurrentsincellsexpressingNR1a/NR2A,butitshowedinhibitoryactivityincellsexpressingNR1a/NR2B receptors andthetriheteromericcombinationofNR1a/NR2A/NR2B.AnAla-richcon-Ganalog,con-G[Q6G/gamma7K/N8A/gamma10A/gamma14A/K15A/S16A/N17A](Ala/con-G,wheregammaisGla),inwhichallnonessential amino acidswerealteredtoAlaresidues,manifestedsubunitspecificitysimilartothatofcon-G,suggestingthatthereplacedresiduesarenotresponsibleforselectivityinthecon-Gframework.Asarcosine-containingcon-Ttruncationanalog,con-T[1-9/G1Src/Q6G],inhibitedcurrentsinNR1a/NR2AandNR1a/NR2Breceptors,eliminatingresidues10-21asmediatorsofthebroadsubunitselectivityofcon-T.Incontrasttothenulleffectsofcon-GandAla/con-GataNR1a/NR2A-containingreceptor,someinhibition(approximately40%)ofNMDA-evokedcurrentswaseffectedbythese peptides incellsexpressingNR1b/NR2A.Thisfindingsuggeststhatthepresenceofexon 5 inNR1bplaysaroleintheactivityoftheconantokins.Analysisofvarious conantokinanalogsdemonstratedthatLeu(5)ofcon-Gisanimportantdeterminantof conantokin selectivity.Takenasawhole,theseresultssuggestthattheimportantmoleculardeterminantsonconantokinsresponsibleforNMDAreceptoractivityandspecificityarediscretelyhousedinspecificresiduesofthese peptides,thusallowingmolecularmanipulationoftheNMDAreceptorinhibitorypropertiesoftheconantokins.
Klein,R.C.,etal.(2001)Theaminoacidresidueatsequenceposition5intheconantokinpeptidespartiallygovernssubunit-selectiveantagonismofrecombinantN-methyl-D-aspartatereceptors, JBiolChem.PMID: 11335724
ConantokinGisanNR2B-selectivecompetitiveantagonistofN-methyl-D-aspartatereceptors.
ConantokinG(ConG)isa17-amino-acidpeptideantagonistofN-methyl-D-aspartate(NMDA)receptorsisolatedfromthevenomofthemarineconesnail,Conusgeographus.ThemechanismofactionofConGhasnotbeenwelldefined;bothcompetitiveandnoncompetitiveinteractionswiththeNMDA-bindingsitehavebeenproposed.InthisstudythemechanismofactionandsubunitselectivityofConGwasexaminedinwhole-cellvoltage-clamprecordingsfromculturedneuronsandintwoelectrodevoltage-clamprecordingsfromXenopusoocytesexpressingrecombinantNMDAreceptors.ConGwasapotentandselectiveantagonistofNMDA-evokedcurrentsinmurinecorticalneurons(IC(50)=480nM).TheslowonsetofConGblockcouldbepreventedbycoapplicationwithhighconcentrationsofNMDAorofthecompetitiveantagonist(RS)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonicacid.Furthermore,inoocytesexpressingNR1a/NR2Breceptors,ConGproducedarightwardshiftintheconcentration-responsecurveforNMDA,providingsupportforacompetitiveinteractionwiththeNMDA-bindingsite.ConGproducedanapparentnoncompetitiveshiftintheconcentration-responsecurveforsperminepotentiationofNMDAresponses,butthiswasduetospermine-inducedenhancementofConGblock.SpermineproducedasimilarenhancementofDL-2-amino-S-phosphopentanoicacidblock.Finally,ConGselectivelyblockedNMDAreceptorscontainingtheNR2Bsubunit.TheseresultsdemonstratethatConGisasubunit-specificcompetitiveantagonistofNMDAreceptors.TheuniquesubunitselectivityprofileofConGmayexplainitsfavorableinvivoprofilecomparedwithnonselectiveNMDAantagonists.
DonevanSD., etal. (2000)ConantokinGisanNR2B-selectivecompetitiveantagonistofN-methyl-D-aspartatereceptors. MolPharmacol. PMID: 10953056
Bindingofcationstoindividualgamma-carboxyglutamateresiduesofconantokin-Gandconantokin-T
Conantokin-G(con-G)andconantokin-T(con-T)arenaturallyoccurringgamma-carboxyglutamate(Gla)-containingpeptidesthatinteractwithmultivalentcationsinfunctionallyrelevantmanners.Selective13C-enrichmentofCgammaandCdeltaineachoftheGlaresidueshasallowedmetalbindingaffinitiestobemeasuredatindividualsidechains.Con-Tpossessestwometalbindingsites,onewithhighaffinityatGla10/Gla14andanotherwithweakbindingatGla3/Gla4.Con-GcontainstwositesofcomparablelowaffinityforCa2+.Analysisofthe13Cline-widthsofcon-GinthepresenceofMg2+allowedtheorderofmetalbindingtobedetermined,withGla10/Gla14loadingbeforetheGla3/Gla4/Gla7cluster.Whilethevariantpeptide,apo-con-T[Lys7Gla],wasshowntohaveaverylowalpha-helicalcontent,thispeptidebindsasecondmetalwithmuchgreateraffinitythanwild-typecon-T.ThisprovidesadditionalevidencethatGla7incon-Gisprimarilyresponsiblefordestabilizingtheapo-form,butisanimportantligandformetalchelation.Theresidue-specificalpha-helicalstabilitiesofcon-Gandcon-Tintheirmetal-freeandmetal-loadedstateswereestimatedbydeterminingratesofprotonexchangefrombackbonepeptidebondamideswithdeuteriumatomsfrom2H20-containingsolvents.Forbothpeptides,thelifetimesofprotonsonseveralpeptidebondamidesincreasedasmetalsofhigheraffinitywereboundtothepeptides,withthelongesthalf-livesfoundintheregionofthealpha-helicalturnstabilizedbytheGla10/Gla14metalcoordinationsite.WeproposethatGla10andGla14constitutetheprimarytightmetalionbindingsiteinbothpeptides.Thisdetailedanalysiswithphysiologicallyrelevantmetalcationsiscrucialfordecipheringtherolesofcriticalaminoacidsinthebioactivityoftheconantokinpeptides.
Blandl,T., etal.(1999)Bindingofcationstoindividualgamma-carboxyglutamateresiduesofconantokin-Gandconantokin-T, JPeptRes. PMID: 10406223
NMDA-receptorantagonistrequirementsinconantokin-G.
Aseriesofvariantsoftheneuroactive17-residuegamma-carboxyglutamate-(Gla)-containingpolypeptide,conantokin-G(con-G),weresynthesizedwiththeintentionofdeterminingthosefeaturesthatwereimportantforitsN-methyl-D-aspartate(NMDA)receptor-targetedantagonistactivityandforadoptionofitsdivalentcation-dependentalpha-helicalconformation.Employingthebindingof[3H]dizolcipine(MK-801)asanassayforopenreceptorionchannelsinratbrainmembranes,whichdisplaysinhibitionbycon-G(IC50=0.48microM),itwasfoundthatreplacementbyanAlaresidueofGla4ledtocompleteinactivationofthepeptide,whereasasimilarreplacementofGla3resultedina20-folddecreasedpotency.AlasubstitutionsforGla10andGla14didnotsubstantiallyaffect[3H]MK-801binding.ThissamesubstitutionatGla7appearedtoslightlyenhancebinding.Alareplacementsofnon-Glaresiduesdemonstratedthatfourofthem,viz.Glu2,Leu5,Gln9,andIle12,possessedatleast200-folddecreasesininhibitorypotency,whereassimilarreplacementsatGly1,Leu11,andArg13resultedinpeptideswith8-to12-foldincreasesintheIC50values.TheremainingaminoacidresiduestestedinthesingleAlareplacementseriesshowednosignificantchangesintheinhibitorycharacteristicsofwild-typecon-G.Additionalstudieswithcarboxyl-terminaltruncatedpeptidesrevealedthatthecarboxyl-terminal4aminoacidswereunimportantforthisactivity.Therewasnostrictcorrelationofinhibitionof[3H]MK-801bindingwiththeabilityofthesepeptidestoformcation-dependentalpha-helices.Peptideswithnotablylowalpha-helicalcontentinthepresenceofthesecationswerelackingatleastone,orboth,ofGla10andGla14.Con-G[Gla3,4,7,10,14E]andcon-G[Gla7,10,14E]weretheonlypeptidesthatremainedinacompletelyrandomconformationuponmetalionaddition.
BlandlT., etal. (1998)NMDA-receptorantagonistrequirementsinconantokin-G. FEBSLett. PMID: 9762921
Conantokin-G:anovelpeptideantagonisttotheN-methyl-D-asparticacid(NMDA)receptor
Conantokin-Gisa17aminoacidpeptideisolatedfromthevenomofthefish-eatingsnailConusgeographuswhichproduceshyperactivitywheninjectedintothebrainsofadultmice.WeshowthatthispeptideisaselectiveN-methyl-D-aspartate(NMDA)antagonistbasedonitsabilitytoblockNMDA-inducedelevationofcGMPinratcerebellarslicesinvitro(IC50=171nM),butnotkainicacid-inducedelevations.ThisinhibitioncouldnotbeovercomebyincreasingtheNMDAconcentration,indicatingnon-competitiveinhibition.Conantokin-Gdisplayednoaffinityforbindingsitesforthienylcyclohexylpiperidine,variousglutamatesubclassesorthoseforseveralotherneurotransmitters/neuromodulators.Thispeptide,however,enhanced[3H]glycinebindingtoratforebrainmembranesbutnottospinalcordmembranes.Theactivityprofileofthepeptideinvariousassaysindicatesthatitisanoveltypeofnon-competitiveNMDAantagonist.
MenaEE.,etal.(1990)Conantokin-G:anovelpeptideantagonisttotheN-methyl-D-asparticacid(NMDA)receptor.NeurosciLett. PMID: 2177176
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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