alpha-Conotoxin GI - 76862-65-2

alpha-Conotoxin GI

Catalog Number: EVT-242219
CAS Number: 76862-65-2
Molecular Formula: C55H80N20O18S4
Molecular Weight: 1437.6 g/mol
The product is for non-human research only. Not for therapeutic or veterinary use.

Product Introduction

Description

Alpha-conotoxin GI is a peptide toxin derived from the venom of the marine cone snail Conus geographus. It is known for its ability to selectively bind to nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels crucial for nerve signal transmission. The specificity of alpha-conotoxin GI for certain nAChR subtypes makes it a valuable neuropharmacological tool for studying these receptors and potentially for developing therapeutic agents157.

Applications in Various Fields

The specificity of alpha-conotoxins for particular nAChR subtypes has led to their use as selective probes for studying receptor subclasses in the nervous system. They have become essential tools for identifying the type and diversity of nAChR subclasses and for understanding the role of these receptors in neurological diseases7.

In the field of drug development, alpha-conotoxins serve as templates for rational drug design strategies aimed at creating pharmaceuticals that target specific nAChR subclasses. Their well-defined structures and high affinity for certain receptor subtypes make them promising leads for the development of analgesics, particularly for treating chronic neuropathic pain278.

Furthermore, studies on the oral absorption and biodistribution of alpha-conotoxins, such as alpha-conotoxin MII and its lipidic analogue, have opened up possibilities for their use as orally administered drugs. Although the blood-brain barrier remains a challenge, the ability of these peptides to cross the gastrointestinal tract suggests potential for systemic therapeutic applications10.

Properties

CAS Number

76862-65-2

Product Name

alpha-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-[(3-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

Molecular Formula

C55H80N20O18S4

Molecular Weight

1437.6 g/mol

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

HWYLVHOPQMLNRJ-NAKBKFBQSA-N

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

Synonyms

alpha-conotoxin GI
conotoxin GI
conotoxin GI, reduced

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

Isomeric SMILES

C[C@H]1C(=O)N[C@H]2CSSC[C@@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC2=O)CCCN=C(N)N)CC3=CN=CN3)CC4=CC(=CC=C4)O)CO)C(=O)N)C(=O)N[C@H](C(=O)N5CCC[C@H]5C(=O)N1)CC(=O)N)NC(=O)[C@H](CCC(=O)O)N
Mechanism of Action

The mechanism of action of alpha-conotoxin GI involves the formation of disulfide bonds that are critical for its structural stability and specificity towards nAChRs. The native isomer of alpha-conotoxin GI, GI(2-7;3-13), adopts a structure primarily comprising a distorted 310 helix, which is essential for its interaction with the nAChR. The binding model suggests that the alpha-subunit binding face of the toxin, which includes residues Cys2, Asn4, Pro5, Ala6, and Cys7, interacts with the alpha and delta subunits of the nAChR. The selectivity face, comprised of Arg9 and His10, further orients the molecule for specific binding1.

Alpha-conotoxin GI and its analogs have been shown to exhibit subtype-specific blockade of nAChRs. For example, alpha-conotoxin GIC is a potent antagonist of the human alpha3beta2 nAChR subtype, displaying high selectivity for neuronal over muscle subtypes34. Similarly, alpha-conotoxin ImI preferentially inhibits homomeric alpha7 and alpha9 receptors, demonstrating the fine-tuned specificity of these toxins5. The three-dimensional structures of alpha-conotoxins, as determined by NMR and X-ray crystallography, provide insights into the molecular features that confer their receptor specificity68.

Method of Synthesis or Extraction
Alpha-Conotoxin GI can be synthesized using solid-phase peptide synthesis (SPPS) or extracted from the venom of cone snails. SPPS involves the stepwise addition of amino acids to a resin-bound peptide chain, followed by cleavage and purification. The yield and efficiency of SPPS depend on the length and complexity of the peptide sequence. Extraction from cone snail venom involves the isolation and purification of the peptide using chromatography techniques. The yield and efficiency of extraction depend on the species of cone snail and the amount of venom available. Environmental and safety considerations must be taken into account when working with cone snail venom, as it can be toxic to humans.
Chemical Structure and Biological Activity
Alpha-Conotoxin GI is a 16-amino acid peptide with a disulfide bond between cysteine residues at positions 2 and 8. It binds to alpha-Conotoxin GI in a competitive manner, blocking the binding of acetylcholine and preventing ion channel opening. Alpha-Conotoxin GI has been shown to have high potency and selectivity for certain subtypes of alpha-Conotoxin GI, making it a valuable tool for studying the function of these receptors.
Biological Effects
Alpha-Conotoxin GI has been shown to have a variety of effects on cell function and signal transduction. It can inhibit neurotransmitter release, modulate synaptic plasticity, and affect ion channel activity. In terms of potential therapeutic effects, alpha-Conotoxin GI has been studied for its role in pain management, addiction treatment, and neurodegenerative diseases. However, it also has potential toxic effects, as it can affect the function of other ion channels and receptors in addition to alpha-Conotoxin GI.
Future Perspectives and Challenges
One of the current limitations in the use and study of alpha-Conotoxin GI is its high cost and limited availability. Possible solutions and improvements include the development of more efficient synthesis methods and the use of recombinant DNA technology to produce the peptide in large quantities. Future trends and prospects in the application of alpha-Conotoxin GI in scientific research include the development of new therapeutic applications and the use of the peptide as a tool for studying the function of alpha-Conotoxin GI in various diseases. However, challenges remain in terms of understanding the potential toxic effects of alpha-Conotoxin GI and developing safe and effective therapeutic applications.

Product FAQ

Q1: How Can I Obtain a Quote for a Product I'm Interested In?
  • To receive a quotation, send us an inquiry about the desired product.
  • The quote will cover pack size options, pricing, and availability details.
  • If applicable, estimated lead times for custom synthesis or sourcing will be provided.
  • Quotations are valid for 30 days, unless specified otherwise.
Q2: What Are the Payment Terms for Ordering Products?
  • New customers generally require full prepayment.
  • NET 30 payment terms can be arranged for customers with established credit.
  • Contact our customer service to set up a credit account for NET 30 terms.
  • We accept purchase orders (POs) from universities, research institutions, and government agencies.
Q3: Which Payment Methods Are Accepted?
  • Preferred methods include bank transfers (ACH/wire) and credit cards.
  • Request a proforma invoice for bank transfer details.
  • For credit card payments, ask sales representatives for a secure payment link.
  • Checks aren't accepted as prepayment, but they can be used for post-payment on NET 30 orders.
Q4: How Do I Place and Confirm an Order?
  • Orders are confirmed upon receiving official order requests.
  • Provide full prepayment or submit purchase orders for credit account customers.
  • Send purchase orders to sales@EVITACHEM.com.
  • A confirmation email with estimated shipping date follows processing.
Q5: What's the Shipping and Delivery Process Like?
  • Our standard shipping partner is FedEx (Standard Overnight, 2Day, FedEx International Priority), unless otherwise agreed.
  • You can use your FedEx account; specify this on the purchase order or inform customer service.
  • Customers are responsible for customs duties and taxes on international shipments.
Q6: How Can I Get Assistance During the Ordering Process?
  • Reach out to our customer service representatives at sales@EVITACHEM.com.
  • For ongoing order updates or questions, continue using the same email.
  • Remember, we're here to help! Feel free to contact us for any queries or further assistance.

Quick Inquiry

 Note: Kindly utilize formal channels such as professional, corporate, academic emails, etc., for inquiries. The use of personal email for inquiries is not advised.