Molecular Biology and Gene Regulation of Vasopressin

Long-Residence Time Peptide Antagonist for the Vasopressin V2 Receptor to Treat Autosomal Dominant Polycystic Kidney Disease

“…N-terminal acylation is often employed in the structure modification of peptide drugs. 27 Thus, we replaced the propionyl acid of peptide 19 at the Nterminal with benzoic acid (28), p-tolylacetic acid (29), 1adamantaneacetic acid (30), and pentadecanoic acid (31). Peptides 29 and 30 showed a high binding affinity to the V 2 R with K i values of 51 ± 7 and 81 ± 12 nM, respectively (Table 4).…”

“…29,30 This subfamily plays critical roles in the regulation of diverse physiological processes, including water homeostasis, blood pressure modulation, and social behavior, with each subtype exhibiting distinct tissue distribution and functional specificity. 31,32 Next, we examined whether compound 33 could act on other vasopressin receptor subtypes. Because V 1A and V 2 receptors are expressed in the kidney, we examined the selectivity of peptide 33 binding to the V 2 R over the V 1A receptor.…”

“…The V 2 R receptor is well-established as a member of the vasopressin/oxytocin receptor subfamily within the G-protein-coupled receptor superfamily, which encompasses four closely related receptor subtypes: V 1A , V 1B , V 2 , and oxytocin receptors. , This subfamily plays critical roles in the regulation of diverse physiological processes, including water homeostasis, blood pressure modulation, and social behavior, with each subtype exhibiting distinct tissue distribution and functional specificity. , Next, we examined whether compound 33 could act on other vasopressin receptor subtypes. Because V 1A and V 2 receptors are expressed in the kidney, we examined the selectivity of peptide 33 binding to the V 2 R over the V 1A receptor.…”

Benzodiazepine Derivatives as Potent Vasopressin V2 Receptor Antagonists for the Treatment of Autosomal Dominant Kidney Disease

“…The endogenous vasopressin can act on four receptor subtypes, namely, the V 1A , V 1B , V 2 , and oxytocin receptors. Given that the V 1A and V 2 receptors, but not V 1B or oxytocin receptor, are abundantly expressed in the kidney, 16 we specifically examined the selectivity of benzodiazepine derivatives binding to the V 2 R over the V 1A R. We found that the affinity of compound 25 for the V 1A R was 147 ± 7 nM, while the affinity of TVP for the V 1A R was 296 ± 36 nM (Figure S1). Thus, compound 25 appeared to be less selective to the V 2 R compared to tolvaptan (16-fold vs 123-fold).…”