ρ-Da1a-AdTx1

Product Name:ρ-Da1a-AdTx1

Purity:95%

Molar Mass:7283.29

Chemical Formula:C310H481N87O100S8

Storage:Store at -20 degrees Celsius

Sequence:LTC3VTSKSIFGITTEDC17PDGQNLC24FKRRHYVVPKIYDSTRGC42AATC46PIPENYDSIHC57C58KTDKC63NE

Target:alpha(1A)-adrenoceptor

Application:

ρ-Da1a (also known as AdTx1) is a peptide toxin isolated from the venom of the green mamba snake (Dendroaspis angusticeps). It is a highly selective antagonist of the α1A-adrenoceptor, a G-protein-coupled receptor involved in the regulation of smooth muscle contraction, particularly in the cardiovascular and urogenital systems. By blocking α1A-adrenoceptors, ρ-Da1a disrupts adrenergic signaling, making it a valuable tool in research focused on understanding the role of these receptors in physiological processes such as blood pressure regulation and urinary tract function. It also has potential therapeutic implications in treating conditions like hypertension and benign prostatic hyperplasia (BPH).

Current Research:

ρ-Da1a, also known as AdTx1, is a 65-amino-acid peptide toxin isolated from the venom of the eastern green mamba (Dendroaspis angusticeps). It belongs to the three-finger toxin family and is stabilized by four disulfide bridges.

Selectivity and Binding

ρ-Da1a exhibits high affinity and specificity for the α₁A-adrenoceptor subtype, with a reported inhibition constant (Kᵢ) of 0.35 nM. It is approximately 1,000 times more potent on α₁A-adrenoceptors than on other adrenoceptor subtypes.

Mechanism of Action

As a selective antagonist, ρ-Da1a binds to the orthosteric site of the α₁A-adrenoceptor, inhibiting the binding of endogenous agonists such as norepinephrine. This interaction prevents receptor activation and subsequent intracellular signaling pathways. Notably, ρ-Da1a displays insurmountable antagonism, indicating that it may induce conformational changes in the receptor that hinder agonist binding even at high agonist concentrations.

Pharmacological Effects

By inhibiting α₁A-adrenoceptors, ρ-Da1a effectively relaxes smooth muscle tissues, particularly in the prostate. This property suggests potential therapeutic applications in conditions like benign prostatic hyperplasia, where α₁A-adrenoceptor antagonism can alleviate symptoms by reducing smooth muscle tone.

Research Applications

Due to its high specificity and potency, ρ-Da1a serves as a valuable tool in pharmacological research:

Receptor Characterization: It aids in studying the structural and functional properties of α₁A-adrenoceptors, enhancing our understanding of their physiological roles.

Drug Development: Insights into its interaction with α₁A-adrenoceptors contribute to the design of novel therapeutics targeting these receptors in various cardiovascular and urological disorders.

Structural Studies

The crystal structure of ρ-Da1a has been determined at a resolution of 1.95 Å, revealing strong similarities to other three-finger toxins from mamba venoms. This structural information provides a basis for understanding its receptor selectivity and mechanism of action.

Conclusion

ρ-Da1a (AdTx1) is a potent and selective antagonist of α₁A-adrenoceptors, offering significant insights into adrenergic signaling and potential therapeutic avenues for related disorders. Its applications extend from fundamental research to the development of novel pharmacological agents.

Reference:

Maïga, A., Merlin, J., Marcon, E., Rouget, C., Larregola, M., Gilquin, B., … & Gilles, N. (2013). Orthosteric binding of ρ-Da1a, a natural peptide of snake venom interacting selectively with the α1A-adrenoceptor. PLoS One, 8(7), e68841.