SNX-482 hasbeenisolatedfromthevenomoftheSpiderHysterocratesgigas(Africantarantula). SNX-482 modulatestheR-type currentassociatedwiththeclassα1Ecalciumchannel(Cav2.3 fromtheCACNA1Egene). SNX-482 antagonizeschannelactivationbyinducingadepolarizingshiftintheactivationpotential,thuspreventingthechannelfromundergoingnormalmembranedepolarization. SNX-482 actsrapidlyandmaintainsitseffect.
Description:
AAsequence: Gly-Val-Asp-Lys-Ala-Gly-Cys7-Arg-Tyr-Met-Phe-Gly-Gly-Cys14-Ser-Val-Asn-Asp-Asp-Cys20-Cys21-Pro-Arg-Leu-Gly-Cys26-His-Ser-Leu-Phe-Ser-Tyr-Cys33-Ala-Trp-Asp-Leu-Thr-Phe-Ser-Asp-OH
Disulfidebonds: Cys7-Cys21,Cys14-Cys26 andCys20-Cys33
Length(aa): 41
Formula: C192H274N52O60S7
MolecularWeight: 4496.42Da
Appearance:Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber: 203460-30-4
Source: Synthetic
Purityrate: >95%
Reference:
TheCav2.3calciumchannelantagoNISTSNX-482reducesdorsalhornneuronalresponsesinaratmodelofchronicneuropathicpain
Neuropathicpainisadifficultstatetotreat,characterizedbyalterationsinsensoryprocessingthatcanincludeallodynia(touch-evokedpain).Evidenceexistsfornervedamage-inducedplasticityinbothtransmission&modulatorysystems,includingchangesinvoltage-dependentcalciumchannel(VDCC)expression&function;however,theroleofCa(v)2.3calciumchannelshasnotclearlybeendefined.Here,theeffectsofSNX-482,aselectiveCa(v)2.3antagonist,onsensorytransmissionatthespinalcordlevelhavebeeninvestigatedintherat.Thespinalnerveligation(SNL)modelofchronicneuropathicpain[Kim&Chung,(1992)Pain,50,355-363]wasusedtoinducemechanicalallodynia,astestedontheipsilateralhindpaw.Invivoelectrophysiologicalmeasurementsofdorsalhornneuronalresponsestoinnocuous&noxiouselectricalandnaturalstimuliweremadeafterSNL&comparedtosham-operatedanimals.SpinalSNX-482(0.5-4microg/50microL)exerteddose-relatedinhibitionsofnoxiousC-fibre-andAdelta-fibre-mediatedneuronalresponsesinconditionsofneuropathy,butnotinsham-operatedanimals.MeasuresofspinalcordhyperexcitABIlity&nociceptionweremostsusceptIBLetoSNX-482.Incontrast,non-noxiousAbeta-mediatedresponseswerenotaffectedbySNX-482.Moreover,responsestoinnocuousmechanical&alsothermalstimuliweremoresensitivetoSNX-482inSNLthancontrolanimals.ThisstudyisthefirsttodemonstrateanantinociceptiveroleforSNX-482-sensitivechannelsindorsalhornneuronsduringneuropathy.ThesedataareconsistentwithplasticityinCa(V)2.3calciumchannelexpressionandsuggestapotentialselectivetargettoreducenociceptivetransmissionduringconditionsofnervedamage.
MatthewsEA., etal.(2007)TheCav2.3calciumchannelantagonistSNX-482reducesdorsalhornneuronalresponsesinaratmodelofchronicneuropathicpain. EurJNeurosci. PMID17610575
SNX482selectivelyblocksP/QCa2+channelsanddelaystheinactivationofNa+channelsofchromaffincells
TheeffectsofthetoxinSXN482onCa2+channelcurrents(ICa),Na+currents(INa),andK+currents(IK)havebeenstudiedinbovineadrenalmedullarychromaffincellsvoltage-clampedat-80mV.Currentswereelicitedbydepolarisingpulsesto0-10mV(ICaandINa)orto+60mV(IK).SNX482blockedICainaconcentration-dependentmanner.Theinhibitioncurveexhibitedtwophases.Thefirsthigh-affinityphasecomprised28%ofthewhole-cellcurrent&exhibitedanIC50of30.2nM.Thesecondlow-affinityphasecomprisedover70%ofICa&hadanIC50of758.6nM.Blockadewasrapidandfullyreversibleuponwashoutofthetoxin.OcclusionexperimentsshowedadditivityofblockadeexertedbynifedipineplusSNX482(0.3microM)andbyomega-conotoxinGVIAplusSNX482.Incontrast,blockadeexertedbycombinedomega-agatoxinIVAplusSNX482(about50%ofthewholecell)didnotshowadditivity.At0.3microMandhigherconcentrations,SNX482delayedtheinactivationofINa.Thetimeconstant(tau)forinactivationofINaincontrolconditionsdoubledinthepresenceof0.5microMSNX482.At0.3microM,SNX482didnotaffectIK.Ourdatademonstratethat:(i)SNX482selectivelyblocksP/QCa2+channelsatsubmicromolarconcentrations;(ii)thetoxinpartiallyblocksNa+channels;(iii)SNX482delaystheinactivationofNa+channels.TheseresultsrevealnovelpropertiesofSNX482andcastdoubtsontheclaimedselectivity&specificityofthetoxintoblocktheR-typeCa2+channel.
ArroyoG, etal.(2003)SNX482selectivelyblocksP/QCa2+channelsanddelaystheinactivationofNa+channelsofchromaffincells, EurJPharmacol. PMID:12954354
InteractionofSNX482withdomainsIIIandIVinhibitsactivationgatingofalpha(1E)(Ca(V)2.3)calciumchannels
Bourinet,E., etal. (2001)InteractionofSNX482withdomainsIIIandIVinhibitsactivationgatingofalpha(1E)(Ca(V)2.3)calciumchannels, Biophys. PMID11423396
SelectivepeptideantagonistoftheclassEcalciumchannelfromthevenomofthetarantulaHysterocratesgigas
WedescribethefirstpotentandselectiveblockeroftheclassECa2+channel.SNX-482,anovel41aminoacidpeptidepresentinthevenomoftheAfricantarantula,Hysterocratesgigas,wasidentifiedthroughitsabilitytoinhibithumanclassECa2+channelsstablyexpressedinamammaliancellline.AnIC50of15-30nMwasobtainedforblockoftheclassECa2+channel,usingeitherpatchclampelectrophysiologyorK+-evokedCa2+flux.Atlownanomolarconcentrations,SNX-482alsoblockedanativeresistantorR-typeCa2+currentinratneurohypophysealnerveterminals,butconcentrationsof200-500nMhadnoeffectonR-typeCa2+currentsinseveraltypesofratcentralneurons.ThepeptidehasthesequenceGVDKAGCRYMFGGCSVNDDCCPRLGCHSLFSYCAWDLTFSD-OHandishomologoustothespiderpeptidesgrammatoxinS1Aandhanatoxin,bothpeptideswithverydifferentionchannelblockingselectivities.NoeffectofSNX-482wasobservedonthefollowingionchannelactivities:Na+orK+currentsinseveralculturedcelltypes(upto500nM);K+currentthroughclonedpotassiumchannelsKv1.1andKv1.4expressedinXenopusoocytes(upto140nM);Ca2+fluxthroughL-andT-typeCa2+channelsinananteriorpituitarycellline(GH3,upto500nM);andBa2+currentthroughclassACa2+channelsexpressedinXenopusoocytes(upto280nM).AweakeffectwasnotedonCa2+currentthroughclonedandstablyexpressedclassBCa2+channels(IC50>500nM).TheuniqueselectivityofSNX-482suggestsitsusefulnessinstudyingthediversity,function,andpharmacologyofclassEand/orR-typeCa2+channels.
Newcomb,R., etal. (1998)SelectivepeptideantagonistoftheclassEcalciumchannelfromthevenomofthetarantulaHysterocratesgigas, Biochemistry. PMID:9799496
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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