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Smartox/Selective blocker of N-type calcium channels/08CON013-01000/1mg
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ω-conotoxinSO-3 isaselectiveblockerofN-typevoltage-sensitivecalciumchannels.EC50 for ω-conotoxinSO-3is 0.16µM(similarto ω-conotoxinMVIIA) onHVAcalciumcurrents. ω-conotoxinSO-3 didnotshowanyinhibitingeffectson L-type,P/Q-typeandR-typecurrentsat3µMconcentration. ω-conotoxinSO-3 hasnoeffectonvoltage-sensitivesodiumcurrents,delayedrectifierpotassiumcurrentsandtransientoutwardpotassiumcurrents.At3µM,theinhibitionamountsofHVA ICa wasverysimilarbetween ω-conotoxinSO-3 and ω-conotoxinMVIIA (~32%).TheirinhibitoryeffectsarealmostfullyreversIBLebuttheirhalf-timeforrecoveryaredifferent(~7.5minfor ω-conotoxinSO-3 and ~4.14minfor ω-conotoxinMVIIA). ω-conotoxinSO-3 displaysananalgesicpotencysimilarto ω-conotoxinMVIIA inarangeofacuteandchronicpainmodelsinrodents,buthaslessadverseeffectscomparedwithidenticaldosagesof ω-conotoxinMVIIAinjectedintrathecally.Description:Productcode:08CON013.Categories:Calciumchannels,Highvoltage-gatedCa2+channels.Tags:Cav2.2,N-type.AAsequence: Cys1-Lys-Ala-Ala-Gly-Lys-Pro-Cys8-Ser-Arg-Ile-Ala-Tyr-Asn-Cys15-Cys16-Thr-Gly-Ser-Cys20-Arg-Ser-Gly-Lys-Cys25-NH2Disulfidebonds: Cys1-Cys16,Cys8-Cys20 andCys15-Cys25Length(aa): 25Formula: C100H166N36O31S6MolecularWeight: 2561.00DaAppearance:WhitelyophilizedsolidSolubility: waterandsalinebufferCASnumber:Source: SyntheticPurityrate: >97%Reference:SO-3,anewO-superfamilyconopeptidederivedfromConusstriatus,selectivelyinhibitsN-typecalciumcurrentsinculturedhippocampalneuronsWhole-cellcurrentsinculturedhippocampalneuronswererecordedtoinvestigatetheeffectsofSO-3,anewO-superfamilyconopeptidederivedfromConusstriatus,onvoltage-sensitivechannels.SO-3hadnoeffectonvoltage-sensitivesodiumcurrents,delayedrectifierpotassiumcurrents,andtransientoutwardpotassiumcurrents.SimilartotheselectiveN-typecalciumchannelblockeromega-conotoxinMVIIA(MVIIA),SO-3couldconcentration-dependentlyinhibitthehighvoltage-activated(HVA)calciumcurrents(I(Ca)).MVIIA(3microM),10microMnimodipine,and0.5microMomega-agatoxinIVA(Aga)couldselectivelyblocktheN-,L-,andP/Q-typeI(Ca),whichcontributedapproximately32,approximately38,andapproximately21%oftheHVAcurrentsinhippocampalneurons,respectively.About31%ofthetotalHVAcurrentswereinhibitedby3microMSO-3.SO-3(3microM)and3microMMVIIAinhibitedtheoverlappingcomponentsofHVAcurrents,whereasnooverlappingcomponentwasinhibitedby3microMSO-3and10microMnimodipine,orby3microMSO-3and0.5microMAga.Also,3microMSO-3hadnoeffectonR-typecurrents.SO-3hadlessinhibitoryeffectsonnon-N-typeHVAcurrentsthanMVIIAathigherconcentrations(30and100microM).TheinhibitoryeffectsofSO-3andMVIIAonHVAcurrentswerealmostfullyreversible.However,therecoveryfromblockbyMVIIAwasmorerapidthanrecoveryfromblockbySO-3.ItisconcludedthatSO-3isanewomega-conotoxinselectivelytargetingN-typevoltage-sensitivecalciumchannels.ConsideringthesignificanceofN-typecalciumchannelsforpaintransduction,SO-3mayhavetherapeuticpotentialasanovelanalgesicagent.Wen,L.,etal.(2005)SO-3,anewO-superfamilyconopeptidederivedfromConusstriatus,selectivelyinhibitsN-typecalciumcurrentsinculturedhippocampalneurons,BrJPharmacol.PMID:15880145EffectofnewO-superfamilyconotoxinSO3onsodiumandpotassiumcurrentsofculturedhippocampalneuronsTheeffectsofanewO-superfamilyconotoxinSO3onsodiumandpotassiumcurrentswereexaminedinculturedrathippocampalneuronsusingthewhole-cellpatchclamptechnique.SO3causedaconcentration-dependent,rapidlydevelopingandreversibleinhibitionofsodiumcurrents(I(Na)).TheIC(50)valuefortheblockageofI(Na)wascalculatedtobe0.49andtheHillcoefficientwas1.7.Usingelectrophysiologicalandpharmacologicalprotocols,transientA-typepotassiumcurrents(I(A))anddelayedrectifierspotassiumcurrents(I(K))wereisolated.SO3causedaconcentration-dependent,andreversibleinhibitionofI(K).TheIC(50)valuefortheblockageofI(K)wascalculatedtobe1.6andtheHillcoefficientwas0.6,withnosignificanteffectonI(A).TheseresultsindicatethatSO3canselectivelyinhibitneuronalsodiumandpotassiumcurrents.Li,Z.,etal.(2003)EffectofnewO-superfamilyconotoxinSO3onsodiumandpotassiumcurrentsofculturedhippocampalneurons,BrainRes.PMID:12591132
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) ”。
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