d[Leu4,Lys8]-VP

Product Name:d[Leu4,Lys8]-VP

CAS No:42061-33-6

Purity:95%

Molar Mass:1026.2

Chemical Formula:C47H67N11O11S2

Storage:Store at -20 degrees Celsius

Sequence:XYFLNCPKG

Target:vasopressin V1B

Application:d[Leu4,Lys8]-VP, also known as d[Leucine4,Lysine8]-Vasopressin, is a synthetic analog of the neuropeptide vasopressin, in which the fourth position leucine and the eighth position lysine are substituted with their d-forms. This modification enhances the compound's stability by making it resistant to enzymatic degradation. d[Leu4,Lys8]-VP acts as a vasopressin receptor antagonist, particularly targeting V1 and V2 receptors. It is commonly used in biochemical research to study vasopressin-related pathways, especially in the fields of cardiovascular, renal, and neuroendocrine studies.

Current Research:

[d-Leu⁴,Lys⁸]-Vasopressin, abbreviated as [d-Leu⁴,Lys⁸]-VP, is a synthetic analog of arginine vasopressin (AVP) engineered to selectively target the V₁b (also known as V₃) receptor subtype. This analog features two key modifications: the substitution of the fourth amino acid with d-leucine and the eighth position with lysine, resulting in the sequence Cys-Tyr-d-Leu-Gln-Asn-Cys-Pro-Lys-Gly-NH₂. These alterations confer high affinity and specificity for the V₁b receptor, distinguishing it from other vasopressin receptor subtypes.

Receptor Specificity and Binding Affinity

Pharmacological studies have demonstrated that [d-Leu⁴,Lys⁸]-VP exhibits potent agonistic activity at the rat V₁b receptor, with negligible effects on V₁a and V₂ receptors. This selectivity is crucial for dissecting the physiological and pathological roles of V₁b receptors, which are predominantly expressed in the anterior pituitary and are involved in the regulation of adrenocorticotropic hormone (ACTH) secretion.

Physiological Implications

Activation of V₁b receptors by [d-Leu⁴,Lys⁸]-VP stimulates the release of ACTH from the anterior pituitary, subsequently influencing cortisol production from the adrenal cortex. This pathway plays a significant role in the body's response to stress. The selective activation of V₁b receptors by this analog allows researchers to investigate the specific contributions of these receptors to the hypothalamic-pituitary-adrenal (HPA) axis function and stress-related disorders.

Research Applications

The development of [d-Leu⁴,Lys⁸]-VP as the first V₁b-selective agonist has provided a valuable tool for:

Elucidating the role of V₁b receptors in the regulation of the HPA axis and their involvement in stress responses.
Investigating the potential therapeutic targeting of V₁b receptors in conditions such as depression and anxiety disorders, where dysregulation of the HPA axis is implicated.
Differentiating the physiological effects mediated by V₁b receptors from those mediated by other vasopressin receptor subtypes.
Conclusion

[d-Leu⁴,Lys⁸]-Vasopressin serves as a potent and selective tool for probing the functions of V₁b receptors in neuroendocrine regulation. Its application in research continues to advance our understanding of vasopressin receptor pharmacology and the development of targeted therapies for stress-related disorders.

Reference:

Pena, A., Murat, B., Trueba, M., Ventura, M. A., Wo, N. C., Szeto, H. H., ... & Manning, M. (2007). Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V1b Receptor: Based on Modifications of Deamino-[Cys] arginine Vasopressin at Positions 4 and 8. Journal of medicinal chemistry, 50(4), 835-847.