Smartox/Hm1a，Nav1.1/HMA001-00100/0.1mg的选择性激动剂
商品编号：
HMA001-00100
品牌：
smartox-biotech
市场价：
¥4368.00
美元价：
3360.00
产品分类：
酸碱缓冲液
联系Q Q：
3392242852
电话号码：
4000-520-616
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info@ebiomall.com
商品介绍
Hm1ahasbeenidentifiedfromthevenomofthespiderHeteroscodramaculata.Hm1ahasbeendescribedasapotentandselectiveagoNISTofthevoltage-gatedsodiumchannelNav1.1withanECvalueof38nM.Nav1.1isexpressedintheCNSandmutationsareassociatedwithseveraldisorderssuchasepilespyorautism.
SmartoxBiotechnologyispleasedtoofferasyntheticandfunctionallyactiveHm1adedicatedtoresearchlaboratoryuseonly.
Description:
AAsequence:ECRYLFGGCSSTSDCCKHLSCRSDWKYCAWDGTFS-OH
Disulfidebonds: Cys2-Cys16,Cys9-Cys21,Cys15-Cys28
Length(aa): 35
Formula: C170H239N47O54S6
MolecularWeight: 3997.46g/mol
CASnumber:
Source: Synthetic
Purityrate: >95%
Reference:
Voltage-gatedsodium(Nav)channelsinitiateactionpotentialsinmostneurons,includingprimaryafferentnervefibresofthepainpathway.Localanaestheticsblockpainthroughnon-specificactionsatallNavchannels,butthediscoveryofselectivemodulatorswouldfacilitatetheanalysisofindividualsubtypesofthesechannelsandtheircontributionstochemical,mechanical,orthermalpain.Hereweidentifyandcharacterizespider(Heteroscodramaculata)toxinsthatselectivelyactivatetheNav1.1subtype,theroleofwhichinnociceptionandpainhasnotbeenelucidated.WeusetheseprobestoshowthatNav1.1-expressingfibresaremodality-specificnociceptors:theiractivationelicitsrobustpainbehaviourswithoutneurogenicinflammationandproducesprofoundhypersensitivitytomechanical,butnotthermal,stimuli.Inthegut,high-thresholdmechanosensitivefibresalsoexpressNav1.1andshowenhancedtoxinsensitivityinamousemodelofirritablebowelsyndrome.Together,thesefindingsestablishanunexpectedroleforNav1.1channelsinregulatingtheexcitABIlityofsensorynervefibresthatmediatemechanicalpain.
TheNav1.1voltage-gatedsodiumchannelisacriticalcontributortoexcitabilityinthebrain,wherepathologicallossoffunctionleadstosuchdisordersasepilepsy,Alzheimer’sdisease,andautism.Thisvoltage-gatedsodium(Nav)channelsubtypealsoplaysanimportantroleinmechanicalpainsignalingbyprimaryafferentsomatosensoryneurons.Therefore,pharmacologicmodulationofNav1.1representsapotentialstrategyfortreatingexcitabilitydisordersofthebrainandperiphery.InactivationisacomplexaspectofNavchannelgatingandconsistsoffastandslowcomponents,eachofwhichmayinvolveacontributionfromoneormorevoltage-sensingdomains.Here,weexploittheHm1aspidertoxin,aNav1.1-selectivemodulator,tobetterunderstandtherelationshipbetweenthesetemporallydistinctmodesofinactivationandaskwhethertheycanbedistinguishedpharmacologically.WeshowthatHm1ainhibitsthegatingmovementofthedomainIVvoltagesensor(VSDIV),hinderingbothfastandslowinactivationandleADIngtoanincreaseinNav1.1availabilityduringhigh-frequencystimulation.Incontrast,ICA-121431,asmall-moleculeNav1.1inhibitor,acceleratesasubsequentVSDIVgatingtransitiontoaccelerateentryintotheslowinactivatedstate,resultinginuse-dependentblock.FurtherevidenceforfunctionalcouplingbetweenfastandslowinactivationisprovidedbyaNav1.1mutantinwhichfastinactivationremovalhascomplexeffectsonslowinactivation.Takentogether,ourdatasubstantiatethekeyroleofVSDIVinNavchannelfastandslowinactivationanddemonstratethatthesegatingprocessesaresequentialandcoupledthroughVSDIV.ThesefindingsprovideinsightintoapharmacophoreonVSDIVthroughwhichmodulationofinactivationgatingcaninhibitorfacilitateNav1.1function.
品牌介绍
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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