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α-Conotoxin MII

* Please kindly note that our products are not to be used for therapeutic purposes and cannot be sold to patients.

α-Conotoxin MII is a nicotinic acetylcholine receptor antagonist. It is highly potent, selective and competitive for α3β2 subunit. Its IC50 value is 0.5-3.5 nM at α3β2 expressed in Xenopus oocytes. It also potently prevents β3-containing neuronal nicotinic receptors.

Category

Peptide Inhibitors

Catalog number

BAT-010338

CAS number

175735-93-0

Molecular Formula

C67H103N23O22S4

Molecular Weight

1710.99

Specification
Reference Reading

IUPAC Name

3-[(1R,6R,9S,12S,15S,18S,21S,24S,27S,30R,33S,36S,42S,45S,50R)-50-[(2-amino-1-hydroxyethylidene)amino]-8,11,14,17,20,23,26,29,32,35,44,47,49-tridecahydroxy-6-(C-hydroxycarbonimidoyl)-12,42-bis(2-hydroxy-2-iminoethyl)-15,45-bis(hydroxymethyl)-18,27-bis(1H-imidazol-5-ylmethyl)-9,24-bis(2-methylpropyl)-41-oxo-33-propan-2-yl-3,4,52,53-tetrathia-7,10,13,16,19,22,25,28,31,34,40,43,46,48-tetradecazatricyclo[28.17.7.036,40]tetrapentaconta-7,10,13,16,19,22,25,28,31,34,43,46,48-tridecaen-21-yl]propanoic acid

Synonyms

Alpha-Conotoxin MII; H-Gly-Cys(1)-Cys(2)-Ser-Asn-Pro-Val-Cys(1)-His-Leu-Glu-His-Ser-Asn-Leu-Cys(2)-NH2; glycyl-L-cysteinyl-L-cysteinyl-L-seryl-L-asparagyl-L-prolyl-L-valyl-L-cysteinyl-L-histidyl-L-leucyl-L-alpha-glutamyl-L-histidyl-L-seryl-L-asparagyl-L-leucyl-L-cysteinamide (2->8),(3->16)-bis(disulfide)

Purity

≥95%

Density

1.5±0.1 g/cm3

Boiling Point

2239.4±65.0°C at 760 mmHg

Sequence

GCCSNPVCHLEHSNLC-NH2 (Disulfide bridge: Cys2 and Cys8, Cys3 and Cys16)

Storage

Store at -20°C

Solubility

Soluble in Water (1 mg/mL)

InChI

InChI=1S/C67H103N23O22S4/c1-29(2)12-35-55(100)77-34(9-10-51(96)97)54(99)80-38(15-33-20-73-28-75-33)58(103)84-41(21-91)60(105)82-39(16-48(69)93)59(104)79-36(13-30(3)4)56(101)86-43(53(71)98)23-113-115-25-45-64(109)85-42(22-92)61(106)83-40(17-49(70)94)67(112)90-11-7-8-47(90)65(110)89-52(31(5)6)66(111)88-46(26-116-114-24-44(62(107)87-45)76-50(95)18-68)63(108)81-37(57(102)78-35)14-32-19-72-27-74-32/h19-20,27-31,34-47,52,91-92H,7-18,21-26,68H2,1-6H3,(H2,69,93)(H2,70,94)(H2,71,98)(H,72,74)(H,73,75)(H,76,95)(H,77,100)(H,78,102)(H,79,104)(H,80,99)(H,81,108)(H,82,105)(H,83,106)(H,84,103)(H,85,109)(H,86,101)(H,87,107)(H,88,111)(H,89,110)(H,96,97)/t34-,35-,36-,37-,38-,39-,40-,41-,42-,43-,44-,45-,46-,47-,52-/m0/s1

InChI Key

DUQYFGMBLOPGBY-XCQLYXDWSA-N

Canonical SMILES

CC(C)CC1C(=NC(C(=NC(C(=NC(C(=NC(C(=NC(C(=NC(CSSCC2C(=NC(C(=NC(C(=O)N3CCCC3C(=NC(C(=NC(CSSCC(C(=N2)O)N=C(CN)O)C(=NC(C(=N1)O)CC4=CN=CN4)O)O)C(C)C)O)CC(=N)O)O)CO)O)C(=N)O)O)CC(C)C)O)CC(=N)O)O)CO)O)CC5=CN=CN5)O)CCC(=O)O)O

1. Alpha-conotoxin MII blocks nicotine-stimulated dopamine release in rat striatal synaptosomes

J M McIntosh, J M Kulak, T A Nguyen, B M Olivera J Neurosci . 1997 Jul 15;17(14):5263-70. doi: 10.1523/JNEUROSCI.17-14-05263.1997.

Activation of presynaptic nicotinic acetylcholine receptors (nAChRs) can induce the release of neurotransmitters such as dopamine and norepinephrine in the CNS. Accumulating evidence suggests that distinct nAChR subtypes are involved; however, it has been difficult to determine the subunit composition of these receptors, in part because of the lack of a sufficient variety of selective nAChR ligands. We present experimental data that at least two different nAChR complexes are involved in dopamine release, one of which has an alpha3/beta2 subunit interface. The recently discovered peptide alpha-conotoxin MII is a potent and selective inhibitor of rat nAChRs containing an interface formed by alpha3 and beta2 subunits. We used this peptide to examine nicotine-stimulated release of dopamine from rat striatal synaptosomes and of norepinephrine from hippocampal synaptosomes. MII (100 nM) blocks 34-49% of the nicotine-stimulated dopamine release, but not dopamine release evoked by elevated [K+]. Furthermore, two peptides structurally related to alpha-conotoxin MII, namely alpha-conotoxin MI (selective for alpha1beta1gammadelta nAChRs) and alpha-conotoxin ImI (selective for alpha7-containing nAChRs), have no effect on nicotine-stimulated dopamine release. The results indicate that one third to half of the dopamine release in the striatal preparation is mediated by nAChRs with an alpha3/beta2 subunit interface. In contrast,

2. [Effect of alpha-conotoxin MII and its N-terminal derivatives on Ca2+ and Na+ signals induced by nicotine in neuroblastoma cell line SH-SY5Y]

L Khiroug, I E Kasheverov, V I Tsetlin, A M Surin, R Tuominen, A S Strukov, O Salminen, M N Zhmak, E V Kriukova, R Talka Bioorg Khim . 2012 Mar-Apr;38(2):214-22. doi: 10.1134/s1068162012020112.

Nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation ofintracellular Ca2+-dependent processes in cells both in normal and pathological states, alpha-Conotoxins isolated from Conus snails venom are a valuable tool for the study of pharmacological properties and functional role of nAChRs. In the present study the alpha-conotoxin MII analogue with the additional tyrosine attached to the N terminus (Y0-MII) was prepared. Also we synthesized analogs with the N-terminal glycine residue labeled with the Bolton- Hunter reagent (BH-MII) or fluorestsein isothiocyanate (FITC-MII). Fluorescence microscopy studies of the neuroblastoma SH-SY5Y cells loaded with Ca2+ indicator Fura-2 or with Ca2+ and Na+ indicators Fluo-4 and SBFI were performed to examine effect of MII modification on its ability to inhibit nicotin-induced increases in intracellular free Ca2+ and Na+ concentrations ([Ca2+] and [Na+]i respectively). Monitoring of individual cell [Ca2+]i and [Na+]i signals revealed different kinetics of [Ca2+]i and [Na+]i rise and decay in responses to brief nicotine (Nic) applications (10-30 microM, 3-5 min), which indicates to different mechanisms of Ca2+ and Na+ homeostasis control in SH-SY5Y cells. MII inhibited in concentration-dependent manner the both [Ca2+]i and [Na+]i increase induced by Nic. Additional tyrosine in the Y0-MII or, especially, more sizeable label in FITC-MII significantly reduced the inhibitory effect of MII. Whereas the efficiency of the Ca2+ response inhibition by BH-MII was found to be close to the efficiency of its inhibition by natural alpha-conotoxin MII, radioiodinated derivatives BH-MII can be used in radioligand assay.

3. Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors in the nucleus accumbens shell regulate progressive ratio responding maintained by nicotine

Darlene H Brunzell, Elizabeth S Hendrick, J Michael McIntosh, Karen E Boschen, Patrick M Beardsley Neuropsychopharmacology . 2010 Feb;35(3):665-73. doi: 10.1038/npp.2009.171.

Beta2 subunit containing nicotinic acetylcholine receptors (beta2(*)nAChRs; asterisk ((*)) denotes assembly with other subunits) are critical for nicotine self-administration and nicotine-associated dopamine (DA) release that supports nicotine reinforcement. The alpha6 subunit assembles with beta2 on DA neurons where alpha6beta2(*)nAChRs regulate nicotine-stimulated DA release at neuron terminals. Using local infusion of alpha-conotoxin MII (alpha-CTX MII), an antagonist with selectivity for alpha6beta2(*)nAChRs, the purpose of these experiments was to determine if alpha6beta2(*)nAChRs in the nucleus accumbens (NAc) shell are required for motivation to self-administer nicotine. Long-Evans rats lever-pressed for 0.03 mg/kg, i.v., nicotine accompanied by light+tone cues (NIC) or for light+tone cues unaccompanied by nicotine (CUEonly). Following extensive training, animals were tested under a progressive ratio (PR) schedule that required an increasing number of lever presses for each nicotine infusion and/or cue delivery. Immediately before each PR session, rats received microinfusions of alpha-CTX MII (0, 1, 5, or 10 pmol per side) into the NAc shell or the overlying anterior cingulate cortex. alpha-CTX MII dose dependently decreased break points and number of infusions earned by NIC rats following infusion into the NAc shell but not the anterior cingulate cortex. Concentrations of alpha-CTX MII that were capable of attenuating nicotine self-administration did not disrupt locomotor activity. There was no effect of infusion on lever pressing in CUEonly animals and NAc infusion alpha-CTX MII did not affect locomotor activity in an open field. These data suggest that alpha6beta2(*)nAChRs in the NAc shell regulate motivational aspects of nicotine reinforcement but not nicotine-associated locomotor activation.