α-Conotoxin GI
Need Assistance?
  • US & Canada:
    +
  • UK: +

α-Conotoxin GI

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

α-conotoxin GI (alpha-conotoxin GI) is a conopeptide that has been isolated from the venom of the cone snail Conus geographus. α-conotoxin GI is a competitive antagonist of the muscle-type nicotinic acetylcholine receptors (nAChR) such as α-conotoxin MI or d-Turbocurarine.

Category
Peptide Inhibitors
Catalog number
BAT-010837
CAS number
76862-65-2
Molecular Formula
C55H80N20O18S4
Molecular Weight
1437.61
α-Conotoxin GI
IUPAC Name
(4S)-4-amino-5-[[(1R,7S,10S,13S,16S,19R,24R,27S,33S,36S,43R)-27-(2-amino-2-oxoethyl)-19-carbamoyl-7-[3-(diaminomethylideneamino)propyl]-16-(hydroxymethyl)-13-[(4-hydroxyphenyl)methyl]-10-(1H-imidazol-5-ylmethyl)-36-methyl-2,5,8,11,14,17,25,28,34,37,44-undecaoxo-21,22,40,41-tetrathia-3,6,9,12,15,18,26,29,35,38,45-undecazatricyclo[22.14.7.029,33]pentatetracontan-43-yl]amino]-5-oxopentanoic acid
Synonyms
Conotoxin GI; Conotoxin G I; alpha-Conotoxin G I; Myotoxin from Conus geographus venom; alpha-Conotoxin G I (reduced), cyclic (2-7),(3-13)-bis(disulfide)
Appearance
White lyophilized solid
Purity
> 95 %
Density
1.71 g/cm3
Sequence
EC(1)C(2)NPAC(1)GRHYSC(2)
Storage
Store at -20°C
Solubility
Water and saline buffer
InChI
InChI=1S/C55H80N20O18S4/c1-25-44(83)72-36-21-95-97-22-37(73-45(84)29(56)9-10-42(80)81)52(91)74-38(51(90)69-33(16-40(57)78)54(93)75-12-4-8-39(75)53(92)65-25)23-96-94-20-35(43(58)82)71-50(89)34(19-76)70-48(87)31(14-26-5-2-6-28(77)13-26)67-49(88)32(15-27-17-61-24-64-27)68-47(86)30(7-3-11-62-55(59)60)66-41(79)18-63-46(36)85/h2,5-6,13,17,24-25,29-39,76-77H,3-4,7-12,14-16,18-23,56H2,1H3,(H2,57,78)(H2,58,82)(H,61,64)(H,63,85)(H,65,92)(H,66,79)(H,67,88)(H,68,86)(H,69,90)(H,70,87)(H,71,89)(H,72,83)(H,73,84)(H,74,91)(H,80,81)(H4,59,60,62)/t25-,29-,30-,31-,32-,33-,34-,35-,36-,37-,38-,39-/m0/s1
InChI Key
CSUQNJQRLCOOSR-NAKBKFBQSA-N
Canonical SMILES
CC1C(=O)NC2CSSCC(C(=O)NC(CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC2=O)CCCN=C(N)N)CC3=CN=CN3)CC4=CC(=CC=C4)O)CO)C(=O)N)C(=O)NC(C(=O)N5CCCC5C(=O)N1)CC(=O)N)NC(=O)C(CCC(=O)O)N
1. Alanine-Scanning Mutagenesis of α-Conotoxin GI Reveals the Residues Crucial for Activity at the Muscle Acetylcholine Receptor
Jie Ren, Yong Wu, Rui Li, Dongting Zhangsun, Jiong Ning, Xiaopeng Zhu, Sulan Luo Mar Drugs . 2018 Dec 13;16(12):507. doi: 10.3390/md16120507.
Recently, the muscle-type nicotinic acetylcholine receptors (nAChRs) have been pursued as a potential target of several diseases, including myogenic disorders, muscle dystrophies and myasthenia gravis, etc. α-conotoxin GI isolated fromConus geographusselectively and potently inhibited the muscle-type nAChRs which can be developed as a tool to study them. Herein, alanine scanning mutagenesis was used to reveal the structure⁻activity relationship (SAR) between GI and mouse α1β1δε nAChRs. The Pro⁵, Gly⁸, Arg⁸, and Tyr11were proved to be the critical residues for receptor inhibiting as the alanine (Ala) replacement led to a significant potency loss on mouse α1β1δε nAChR. On the contrary, substituting Asn⁴, His10and Ser12with Ala respectively did not affect its activity. Interestingly, the [E1A] GI analogue exhibited a three-fold potency for mouse α1β1δε nAChR, whereas it obviously decreased potency at rat α9α10 nAChR compared to wildtype GI. Molecular dynamic simulations also suggest that loop2 of GI significantly affects the interaction with α1β1δε nAChR, and Tyr11of GI is a critical residue binding with three hydrophobic amino acids of the δ subunit, including Leu93, Tyr95and Leu103. Our research elucidates the interaction of GI and mouse α1β1δε nAChR in detail that will help to develop the novel analogues of GI.
2. alpha-Conotoxin GI benzoylphenylalanine derivatives. (1)H-NMR structures and photoaffinity labeling of the Torpedo californica nicotinic acetylcholine receptor
Jonathan B Cohen, Innokenty V Maslennikov, David C Chiara, Yuri N Utkin, Igor E Kasheverov, Vladimir S Pashkov, Victor I Tsetlin, Alexander S Arseniev, Maxim N Zhmak FEBS J . 2006 Apr;273(7):1373-88. doi: 10.1111/j.1742-4658.2006.05161.x.
alpha-Conotoxins are small peptides from cone snail venoms that function as nicotinic acetylcholine receptor (nAChR)-competitive antagonists differentiating between nAChR subtypes. Current understanding about the mechanism of these selective interactions is based largely on mutational analyses, which identify amino acids in the toxin and nAChR that determine the energetics of ligand binding. To identify regions of the nAChR involved in alpha-conotoxin binding by use of photoactivated cross-linking, two benzoylphenylalanine (Bpa) analogs of alpha-conotoxin GI, GI(Bpa12) and GI(Bpa4), were synthesized by replacing the respective residues with Bpa, and their (1)H-NMR structures were determined. Both analogs preserved the GI conformation, but only GI(Bpa12) displaced (125)I-labeled GI from the Torpedo californica nAChR. (125)I-labeled GI(Bpa12) bound to two sites on the receptor (K(d) 13 and 1800 nM), and on UV irradiation specifically photolabeled the alpha, gamma and delta subunits. Photolabeling sites were mapped by selective proteolysis and enzymatic deglycosylation, combined with SDS/PAGE, HPLC and Edman degradation. In the alpha subunit, cobratoxin-inhibited incorporation was limited to the 22-kDa fragment beginning at alphaSer173 and containing the agonist-binding site segment C. In the gamma subunit, radioactivity was localized to two distinct peptides containing agonist-binding site segments F and D: nonglycosylated 24-kDa and glycosylated 13-kDa fragments starting at gammaAla167 and gammaAla49, respectively. The labeling of these fragments is discussed in terms of a model of GI(Bpa12) bound to the extracellular domain of the Torpedo nAChR homology model derived from the cryo-electron microscopy structure of Torpedo marmorata nAChR and X-ray crystal structures of snail acetylcholine-binding protein complexes with agonists and antagonists.
3. Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives
E Atherton, R C Sheppard, B L Stone, J Alford, B M Olivera, A Reyes, F A Luque, M McIntosh, R Galyean, W R Gray Biochemistry . 1984 Jun 5;23(12):2796-802. doi: 10.1021/bi00307a040.
The 13 amino acid toxic peptide from the marine snail Conus geographus, conotoxin GI, blocks the acetylcholine receptor at the neuromuscular junction. In this report, we describe a method for analyzing disulfide bonding in nanomole amounts of small cystine-rich peptides. The procedure involves partial reduction and a double-label alkylation of cysteine residues. Using this method, we show that the natural conotoxin GI has a (2-7, 3-13) disulfide configuration. The structure of conotoxin GI has been confirmed by chemical synthesis. The preparation and purification of molecularly homogeneous, iodinated derivatives of this toxin are also described. All derivatives, including the [diiodohistidine,diiodotyrosine]conotoxin GI, retained at least half of the biological activity of unmodified toxin. Since the tetraiodinated toxin, which is greater than 25% by weight iodine, retains considerable toxicity, unmodified histidine and tyrosine residues in conotoxin GI are not crucial for biological activity.
Online Inquiry
Verification code
Inquiry Basket