Waglerin-1

Product Name:Waglerin-1

Purity:95%

Molar Mass:2520

Chemical Formula:C112H175N37O26S2

Storage:Store at -20 degrees Celsius

Sequence:GGKPDLRPCHPPCHYIPRPKPR

Target:nAChR, GABA(A) receptors

Application:

Waglerin-1 is a peptide toxin derived from the venom of the Wagler’s pit viper (Tropidolaemus wagleri). This toxin specifically targets and inhibits nicotinic acetylcholine receptors (nAChRs), particularly those found in skeletal muscle (the α1 subunit). By blocking these receptors, Waglerin-1 disrupts neuromuscular transmission, leading to muscle paralysis. It has been widely used in research to study the function of nAChRs and to investigate neuromuscular signaling. Additionally, Waglerin-1’s high specificity makes it a valuable tool for understanding receptor pharmacology and exploring therapeutic avenues for conditions related to muscle control and nAChR dysregulation.

Current Research:

Waglerin-1 is a 22-amino-acid peptide toxin isolated from the venom of the Wagler's pit viper (Tropidolaemus wagleri), a snake species native to Southeast Asia. This peptide functions as a competitive antagonist of muscle-type nicotinic acetylcholine receptors (nAChRs), particularly targeting the adult form of these receptors.

Mechanism of Action

Waglerin-1 exhibits high affinity for the ε subunit of muscle nAChRs, binding predominantly at the α/ε subunit interface. This interaction inhibits acetylcholine binding, thereby blocking synaptic transmission at the neuromuscular junction. Notably, Waglerin-1 binds approximately 2,100 times more tightly to the α/ε interface than to the α/δ interface of the mouse nAChR.

Pharmacological Effects

The blockade of nAChRs by Waglerin-1 leads to neuromuscular paralysis, which can result in respiratory failure and death in envenomated prey. Additionally, Waglerin-1 has been reported to modulate GABA_A receptors, though with less potency compared to its effects on nAChRs.

Research Applications

Due to its specificity and potency, Waglerin-1 serves as a valuable tool in neuropharmacological research:

Receptor Characterization: It aids in elucidating the structural and functional dynamics of muscle-type nAChRs, particularly the role of the ε subunit in receptor assembly and function.

Drug Development: Insights into its interaction with nAChRs contribute to the design of novel therapeutics for neuromuscular disorders and conditions involving dysfunctional cholinergic signaling.

Cosmetic Applications

Synthetic analogs of Waglerin-1, such as the tripeptide derivative known as SYN-AKE, have been developed for cosmetic use. These compounds are marketed as anti-wrinkle agents, purportedly mimicking the muscle-relaxing effects of Waglerin-1 to reduce facial wrinkles. However, scientific evidence supporting the efficacy of these products is limited.

Conclusion

Waglerin-1 is a potent peptide toxin that selectively inhibits muscle-type nAChRs, providing significant insights into neuromuscular transmission and potential therapeutic avenues for related disorders. Its applications extend from fundamental research to the development of novel pharmacological and cosmetic agents.

Reference:

Molles, B. E., Tsigelny, I., Nguyen, P. D., Gao, S. X., Sine, S. M., & Taylor, P. (2002). Residues in the ε subunit of the nicotinic acetylcholine receptor interact to confer selectivity of Waglerin-1 for the α− ε subunit interface site. Biochemistry, 41(25), 7895-7906.