μ-ConotoxinPIIIA (mu-conotoxinPIIIA)isaconotoxinthathasbeenisolatedfromthevenomoftheconeConuspurpurascens. μ-conotoxinPIIIA demonstratesahigheraffinityforthemammalianmusclesodiumchannel Nav1.4 (IC50 ~44nM)thanfortheCNSNav1.2subtype(IC50 ~640 nm). μ-ConotoxinPIIIA blocks more irreversIBLyamphibian muscle sodium channels thanmammalianones.
Description:
AAsequence: H-pGlu-Arg-Leu-Cys4-Cys5-Gly-Phe-Hyp-Lys-Ser-Cys11-Arg-Ser-Arg-Gln-Cys16-Lys-Hyp-His-Arg-Cys21-Cys22-NH2
(DisulfidebondsbetweenCys4-Cys16,Cys5-Cys21 andCys11-Cys22)
Length(aa): 22
Formula: C103H165N40O28S6
MolecularWeight: 2604.10Da
Appearance:Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber:
Source: Synthetic
Purityrate: >97%
Reference:
Mechanismofμ-ConotoxinPIIIABindingtotheVoltage-GatedNa+ChannelNaV1.4
Severalsubtypesofvoltage-gatedNa+(NaV)channelsareimportanttargetsforpainmanagement.μ-ConotoxinsisolatedfromvenomsofconesnailsarepotentandspecificblockersofdifferentNaVchannelisoforms.Theinhibitoryeffectofμ-conotoxinsonNaVchannelshasbeenexaminedextensively,butthemechanismoftoxinspecificityhasnotbeenunderstoodindetail.Heretheknownstructureofμ-conotoxinPIIIAandamodeloftheskeletalmusclechannelNaV1.4areusedtoelucidateelementsthatcontributetothestructuralbasisofμ-conotoxinbindingandspecificity.ThemodelofNaV1.4isconstructedbasedonthecrystalstructureofthebacterialNaVchannel,NaVAb.Sixdifferentbindingmodes,inwhichthesidechainofeachofthebasicresiduescarriedbythetoxinprotrudesintotheselectivityfilterofNaV1.4,areexaminedinatomicdetailusingmoleculardynamicssimulationswithexplicitsolvent.Thedissociationconstants(Kd)computedfortwoselectedbindingmodesinwhichLys9orArg14fromthetoxinprotrudesintothefilterofthechannelarewithin2fold;bothvaluesincloseproximitytothosedeterminedfromdoseresponsedatafortheblockofNaVcurrents.ToexplorethemechanismofPIIIAspecificity,adoublemutantofNaV1.4mimickingNaVchannelsresistanttoμ-conotoxinsandtetrodotoxinisconstructedandthebindingofPIIIAtothismutantchannelexamined.ThedoublemutationcausestheaffinityofPIIIAtoreducebytwoordersofmagnitude.
ChenR., etal.(2014) Mechanismofμ-ConotoxinPIIIABindingtotheVoltage-GatedNa+ChannelNaV1.4. PLoSOne. PMID24676211
Solutionstructureofmu-conotoxinPIIIA,apreferentialinhibitorofpersistenttetrodotoxin-sensitivesodiumchannels
Mu-conotoxinsarepeptideinhibitorsofvoltage-sensitivesodiumchannels(VSSCs).Syntheticformsofmu-conotoxinsPIIIAandPIIIA-(2-22)werefoundtoinhibittetrodotoxin(TTX)-sensitiveVSSCcurrentbuthadlittleeffectonTTX-resistantVSSCcurrentinsensoryganglionneurons.Inratbrainneurons,thesepeptidespreferentiallyinhibitedthepersistentoverthetransientVSSCcurrent.RADIoligandbindingassaysrevealedthatPIIIA,PIIIA-(2-22),andmu-conotoxinsGIIIBdiscriminatedamongTTX-sensitiveVSSCsinratbrain,thattheseandGIIICdiscriminatedamongthecorrespondingVSSCsinhumanbrain,andGIIIAhadlowaffinityforneuronalVSSCs.(1)HNMRstudiesfoundthatPIIIAadoptstwoconformationsinsolutionduetocis/transisomerizationathydroxyproline8.Themajortransconformationresultsinathree-dimensionalstructurethatissignificantlydifferentfromthepreviouslyidentifiedconformationofmu-conotoxinsGIIIAandGIIIBthatselectivelytargetTTX-sensitivemuscleVSSCs.ComparisonofthestructuresandactivityofPIIIAtomuscle-selectivemu-conotoxinsprovidesaninsightintothestructuralrequirementsforinhibitionofdifferentTTX-sensitivesodiumchannelsbymu-conotoxins.
Nielsen,K.J., etal. (2002)Solutionstructureofmu-conotoxinPIIIA,apreferentialinhibitorofpersistenttetrodotoxin-sensitivesodiumchannels, JBiolChem. PMID: 12006587
Distinctionamongneuronalsubtypesofvoltage-activatedsodiumchannelsbymu-conotoxinPIIIA
Thefunctionalpropertiesofmostsodiumchannelsaretoosimilartopermitidentificationofspecificsodiumchanneltypesunderlyingmacroscopiccurrent.Suchdiscriminationwouldbeparticularlyadvantageousinthenervoussysteminwhichdifferentsodiumchannelfamilyisoformsarecoexpressedinthesamecell.Totestwhethermembersofthemu-conotoxinfamilycandiscriminateamongknownneuronalsodiumchanneltypes,weexaminedsixtoxinsfortheirABIlitytoblockdifferenttypesofheterologouslyexpressedsodiumchannels.PIIIAmu-conotoxinblockedratbraintypeII/IIA(rBII/IIA)andskeletalmusclesodiumcurrentatconcentrationsthatresultedinonlyslightinhibitionofratperipheralnerve(rPN1)sodiumcurrent.RecordingsfromvariantlinesofPC12cells,whichselectivelyexpresseitherrBII/IIAorrPN1channelsubtypes,verifiedthatthedifferentialblockbyPIIIAalsoappliedtonativesodiumcurrent.ThesensitivitytoblockbyPIIIAtoxinwasthenusedtodiscriminatebetweenrBII/IIAandrPN1sodiumcurrentsinNGF-treatedPC12cellsinwhichbothmRNAsareinduced.Duringthefirst24hrofNGF-treatment,PN1sodiumchannelsaccountedforover90%ofthesodiumcurrent.However,overtheensuing48hrperiod,asharpriseintheproportionofrBII/IIAsodiumcurrentoccurred,confirmingtheidea,basedonpreviousmRNAmeasurements,thattwodistinctsodiumchanneltypesappearsequentiallyduringneuronaldifferentiationofPC12cells.
Safo,P., etal. (2000)Distinctionamongneuronalsubtypesofvoltage-activatedsodiumchannelsbymu-conotoxinPIIIA, JNeurosci. PMID: 10627583
mu-ConotoxinPIIIA,anewpeptidefordiscriminatingamongtetrodotoxin-sensitiveNachannelsubtypes
Wereportthecharacterizationofanewsodiumchannelblocker,mu-conotoxinPIIIA(mu-PIIIA).Thepeptidehasbeensynthesizedchemicallyanditsdisulfidebridgingpatterndetermined.Thestructureofthenewpeptideis:[sequence:seetext]whereZ=pyroglutamateandO=4-trans-hydroxyproline.WedemonstratethatArginine-14(Arg14)isakeyresidue;substitutionbyalaninesignificantlydecreasesaffinityandresultsinatoxinunabletoblockchannelconductancecompletely.Thus,likealltoxinsthatblockatSiteI,mu-PIIIAhasacriticalguanidiniumgroup.Thispeptideisofexceptionalinterestbecause,unlikethepreviouslycharacterizedmu-conotoxinGIIIA(mu-GIIIA),itirreversiblyblocksamphibianmuscleNachannels,providingausefultoolforsynapticelectrophysiology.FurThermore,thediscoveryofmu-PIIIApermitstheresolutionoftetrodotoxin-sensitivesodiumchannelsintothreecategories:(1)sensitivetomu-PIIIAandmu-conotoxinGIIIA,(2)sensitivetomu-PIIIAbutnottomu-GIIIA,and(3)resistanttomu-PIIIAandmu-GIIIA(examplesineachcategoryareskeletalmuscle,ratbrainTypeII,andmanymammalianCNSsubtypes,respectively).Thus,mu-conotoxinPIIIAprovidesakeyforfurtherdiscriminatingpharmacologicallyamongdifferentsodiumchannelsubtypes.
Shon,K.J., etal. (1998)mu-ConotoxinPIIIA,anewpeptidefordiscriminatingamongtetrodotoxin-sensitiveNachannelsubtypes, JNeurosci. PMID: 9614224
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常用流动相加酸碱后PH的总结，希望大家能够提供一点自己测过的结果，谢谢先
1.直接用固体磷酸钠配制成50mM的磷酸钠溶液，再调pH到7.4；（我们试着用这个做了下，发现挂不上柱）
2.配置磷酸钠盐缓冲液：按NaH2PO4：Na2HPO4以19：81的摩尔比配制成pH7.4的缓冲液？（附一张百度出来的配方
）
3.如果是磷酸钠盐缓冲液，可以直接将50mM的NaH2PO4的水溶液用NaOH调成pH7.4吗？
再者，2和3这两个方法配制的磷酸钠盐缓冲液有什么区别？最终效果是一样的吗？如果不一样，有什么理论的知识支撑呢？个人感觉是分析化学中酸碱理论中的缓冲液那里的知识。求帮忙解答这些疑问。
另外，我还想问一下，pH对于Ni柱对His-tagged的蛋白的分离纯化影响大吗？是怎么影响的？谢谢大家了！
有了源数据之后把源数据按照大小排列，
选中源数据区域-->ALT+A1-->选中图标区右键-->更改图表类型-->散点图
因为是考察不同PH对药物的影响，样品又不好改变其PH值，这种情况怎么办？希望有经验的高手指教。
我的流动相是甲醇-水（90：10）
谢谢赐教！
请进子版按格式发贴，自行修改，谢谢。
由弱酸及其盐、弱碱及其盐组成的混合溶液，能在一定程度上抵消、减轻外加强酸或强碱对溶液酸碱度的影响，从而保持溶液的pH值相对稳定。这种溶液称为缓冲溶液。
:)
我在做一细菌不同酸碱度生长状况时,发现这些奇怪现象:pH=3的培养基灭菌(TSB液体培养基)灭菌后pH上升到到9.2!而原来pH=9.0的降到8.7(基本没多少变化),请问各位大侠,这是什么原因?
一般做不同酸碱度生长实验时,该如何才能防止pH在湿热灭菌后基本不变化?
是否可以理解为纯化水得PH范围为6.3-7.6？能否直接用pH计测量？谢谢!
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