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蚂蚁淘在线 / 品牌中心 / Smartox / Smartox//MAM001-00050/0.05毫克

Smartox//MAM001-00050/0.05毫克

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￥2496.00

货号：MAM001-00050

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商品描述

ASIC1a&1bchannelblocker

Mambalgin-1wasinitiallyisolatedbySylvieDiochotandcollaboratorsfromthevenomoftheblackmamba(Dendroaspispolylepispolylepis).Mambalgin-1isapotentandselectiveblockerofacid-sensingionchannels(ASIC).ASICchannelshavebeendemonstratedtobeimpliedinpainpathwaysandappeartobepromisingtherapeutictargets. Mambalgin-1rapidlyandreversIBLyinhibitsrecombinanthomomericASIC1a(IC₅₀=55nM)andheteromericASIC1a+ASIC2a(IC₅₀=246nM)orASIC1a+ASIC2bchannels(IC₅₀=61nM)butalsohumanchannelshASIC1b(IC₅₀=192nM)and hASIC1a+hASIC1b(IC₅₀=72nM).

Mambalgin-1belongstothefamilyofthree-fingertoxinsandhasnosequence/structuralhomologywitheitherPcTx1orAPETx2.Mambalgin-1differsfrommambalgin-2byoneaminoacid.Bothhavedemonstratedasimilaractivity.Mambalgin-1hasnoeffectonASIC2a,ASIC3,ASIC1a+ASIC3andASIC1b+ASIC3channels,aswellasonTRPV1,P2X2,5-HT3A,Nav1.8,Cav3.2andKv1.2channels.

Recentlyquoted

mambalgin-1-bioassay

Fig1: Dose-responsecurveoftheeffectofsyntheticMambalgin-1#MAM001onASIC1acurrentrecordedin Xenopusoocytes.Inthissystem,anIC₅₀of21nMwasdetermined.

Description:

Productcode:MAM001.Category:ASICchannels.Tags:acidsensing,apetx2,ASIC,pain,PcTx1,psalmotoxin.

AAsequence:LKC³YQHGKVVTC¹²HRDMKFC¹⁹YHNTGMPFRNLKLILQGC³⁷SSSC⁴¹SETENNKC⁴⁹C⁵⁰STDRC⁵⁵NK-OH
Disulfidebonds:Cys³-Cys¹⁹,Cys¹²-Cys³⁷,Cys⁴¹-Cys⁴⁹,Cys⁵⁰-Cys⁵⁵
Length(aa):57
Formula: C₂₇₂H₄₂₉N₈₅O₈₄S₁₀MolecularWeight: 6554.59Da
Appearance:whitelyophilizedsolid
Solubility: waterorsalinebuffer
CASnumber:notavailable
Source:synthetic
Purityrate: >98%

Reference:

Blackmambavenompeptidestargetacid-sensingionchannelstoabolishpain.

DiochotS.,etal.(2012)Blackmambavenompeptidestargetacid-sensingionchannelstoabolishpain.Nature.PMID:23034652

Polypeptidetoxinshaveplayedacentralpartinunderstandingphysiologicalandphysiopathologicalfunctionsofionchannels.Inthefieldofpain,theyledtoimportantadvancesinbasicresearchandeventoclinicalapplications.Acid-sensingionchannels(ASICs)aregenerallyconsideredprincipalplayersinthepainpathway,includinginhumans.AsnaketoxinactivatingperipheralASICsinnociceptiveneuronshasbeenrecentlyshowntoevokepain.Hereweshowthatanewclassofthree-fingerpeptidesfromanothersnake,theblackmamba,isabletoabolishpainthroughinhibitionofASICsexpressedeitherincentralorperipheralneurons.Thesepeptides,whichwecallmambalgins,arenottoxicinmicebutshowapotentanalgesiceffectuponcentralandperipheralinjectionthatcanbeasstrongasmorphine.Thiseffectis,however,resistanttonaloxone,andmambalginscausemuchlesstolerancethanmorphineandnorespiratorydistress.PharmacologicalinhibitionbymambalginscombinedwiththeuseofknockdownandknockoutanimalsindicatesthatblockadeofheteromericchannelsmadeofASIC1aandASIC2asubunitsincentralneuronsandofASIC1b-containingchannelsinnociceptorsisinvolvedintheanalgesiceffectofmambalgins.Thesefindingsidentifynewpotentialtherapeutictargetsforpainandintroducenaturalpeptidesthatblockthemtoproduceapotentanalgesia.

CharacterizationofhASIC1achannelsupontoxinmambalgin-1bindinginlivemammaliancells

WenM.,etal. (2015)Site-specificfluorescencespectrumdetectionandcharacterizationofhASIC1achannelsupontoxinmambalgin-1bindinginlivemammaliancells.ChemCommun.PMID: 25873388

Thesynthesisoffluorescentunnaturalamino-acidAnapwasoptimizedandtheAnapwasincorporatedintofoursitesinanacid-pocketoratransmembraneregionofhumanacid-sensingionchannel-1a(hASIC1a).CombinationalAnapfluorescencespectraandpatch-clampelectrophysiologydataillustratedsite-specificconformationalresponsesupontoxinmambalgin-1binding.Thiscombinationalapproachcanbeusedtoanalyseconformationalpropertiesofmanydifferenteukaryoticproteinsintheirfunctionalstates,inasite-specificmannerinlivemammaliancells.

Bindingsiteandinhibitorymechanismofthemambalgin-2

SalinasM.,etal.(2014)Bindingsiteandinhibitorymechanismofthemambalgin-2pain-relievingpeptideonacid-sensingionchannel1a.JBC.PMID:24695733

Acid-sensingionchannels(ASICs)areneuronalproton-gatedcationchannelsassociatedwithnociception,fear,depression,seizure,andneuronaldegeneration,suggestingrolesinpainandneurologicalandpsychiatricdisorders.Wehaverecentlydiscoveredblackmambavenompeptidescalledmambalgin-1andmambalgin-2,whicharenewthree-fingertoxinsthatspecificallyinhibitwiththesamepharmacologicalprofileASICchannelstoexertstronganalgesiceffectsinvivo.Wenowcombinedbioinformaticsandfunctionalapproachestouncoverthemolecularmechanismofchannelinhibitionbythemambalgin-2pain-relievingpeptide.Mambalgin-2bindsmainlyinaregionofASIC1ainvolvingtheupperpartofthethumbdomain(residuesAsp-349andPhe-350),thepalmdomainofanadjacentsubunit,andtheβ-balldomain(residuesArg-190,Asp-258,andGln-259).Thisregionoverlapswiththeacidicpocket(pHsensor)ofthechannel.ThepeptideexertsbothstimulatoryandinhibitoryeffectsonASIC1a,andweproposeamodelwheremambalgin-2trapsthechannelinaclosedconformationbyprecludingtheconformationalchangeofthepalmandβ-balldomainsthatfollowsprotonactivation.ThesedatahelptounderstandinhibitionbymambalginsandprovidecluesforthedevelopmentofnewoptimizedblockersofASICchannels.

Smartox产品货号抗原产品名称应用产品规格产品品牌参考价格折扣价格11CON014-00500Lys-conopressin-G Vasopressin-like peptide0Smartox-Biotech电议请咨询CRO002Cy3-Crotamine Fluorescent tumor-cell specific agent0Smartox-Biotech电议请咨询MEL01Melittin Highly pure synthetic Melittin0Smartox-Biotech电议请咨询11CAS001-01000Morphiceptin Agonist of µ-opoid receptor0Smartox-Biotech电议请咨询011PUR001-00100Purotoxin-1 Selective inhibitor of P2X3 receptors0Smartox-Biotech电议请咨询CRO001Crotamine Cell-penetrating peptide and ion channels blocker0Smartox-Biotech电议请咨询ADT001-00010ρ-Da1a – AdTx1 Selective antagonist of the alpha(1A)-adrenoceptor0Smartox-Biotech电议请咨询ECH001Echistatin α1 isoform0Smartox-Biotech电议请咨询MTX007-00100MT7 – Muscarinic Toxin 7 Blocker of M1-subtype of muscarinic receptor0Smartox-Biotech电议请咨询CON022-00100Rho-Conotoxin-TIA Blocker of α1-adrenoreceptor0Smartox-Biotech电议请咨询13PCT001-00100Psalmotoxin-1 / PcTx1 ASIC1a selective blocker0Smartox-Biotech电议请咨询NMB001-00100NMB-10Smartox-Biotech电议请咨询10OBT001-00100Obtustatin Inhibitor of the binding of α1β1 integrin to collagen IV0Smartox-Biotech电议请咨询08CON009-00500Conantokin-G Selective inhibitor of NR2B-containing NMDAR0Smartox-Biotech电议请咨询MAM001-50010Mambalgin-1 ASIC1a & 1b channel blocker0Smartox-Biotech电议请咨询CON019-50100α-conotoxin-GID Blocker of α3β2, α7 and α4β2 nAChRs0Smartox-Biotech电议请咨询08CON012-00500α-conotoxin-MI Blocks the α/δ site of the muscle-type nAChR0Smartox-Biotech电议请咨询12WAG001-01000Waglerin-1 Waglerin-1 blocks muscle-type nAChRs0Smartox-Biotech电议请咨询WAG002-01000Waglerin-1-FAM Waglerin-1 blocks muscle nAChRs0Smartox-Biotech电议请咨询08GSM001-00050GsMTx4 Selective blocker of mechanosensitive ion channels0Smartox-Biotech电议请咨询MTX002MitTx MitTx toxin – ASIC1a/1b agonist0Smartox-Biotech电议请咨询CON023α-Conotoxin PIA0Smartox-Biotech电议请咨询CBT001alpha-cobratoxin α7 nicotinic acetylcholine receptor (nAChR) antagonist0Smartox-Biotech电议请咨询08CON011-00500α-conotoxin-IMI α7 nAChR selective blocker0Smartox-Biotech电议请咨询CON024-00100α-Conotoxin BuIA0Smartox-Biotech电议请咨询08CON015-00500α-conotoxin-GI Blocks the α/δ site of the muscle-type nAChR0Smartox-Biotech电议请咨询10GTX002-00100GaTx2 Selective blocker of ClC2 (CLCN2) chloride channels0Smartox-Biotech电议请咨询13CON017-00100α-conotoxin-PeIA Discriminates between α9α10 and α7 nAChRs0Smartox-Biotech电议请咨询07APE002-00100APETx2 ASIC3 selective inhibitor0Smartox-Biotech电议请咨询13CON016-00100αC-Conotoxin-PrXA Selective blocker of muscular nACh receptors0Smartox-Biotech电议请咨询

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