Hechter, Oscar; Terada, Shigeyuki; Spitsberg, Vitaly; Nakahara, Tatsuo; Nakagawaga, S. Hase; Flouret, George published the artcile< Neurohypophyseal hormone-responsive renal adenylate cyclase. III. Relationship between affinity and intrinsic activity in neurohypophyseal hormones and structural analogs>, Synthetic Route of 112-63-0, the main research area is neurohyophyseal hormone structure activity; vasopressin receptor adenyl cyclase; oxytocin structure activity; kidney adenyl cyclase vasopressin.
Binding and adenylate cyclase [9012-42-4] activation with neurohypophyseal hormones (NHH) and synthetic analogs were examined in 2 bovine renal medullary membrane preparations The relation between binding affinity of NHH and 10 analogs (as determined by competitive binding studies with 3H-labeled 8-lysine vasopressin (I) [50-57-7] and adenylate cyclase activation) was studied in 1 membrane preparation under identical conditions where hormonal stimulation of cyclase was at steady state and binding was at (or near) equilibrium A linear relation was demonstrated between the neg. logs of peptide concentration required for half-maximal binding and for half-maximal enzyme activation (Ka). Study of adenylate cyclase activation by NHH analogs, with and without a preliminary preincubation, showed that the magnitude of enzyme stimulation achieved (percentage of Vmax relative to I) with certain low affinity analogs was increased when these peptides were assayed without preincubation (in the 0-10-min period) without significant influence on Ka. To maximize the magnitude of adenylate cyclase stimulation achieved with low affinity analogs, the relation between the apparent affinity and intrinsic activity of 30 NHH analogs was studied in a 2nd membrane, where adenylate cyclase was assayed without preincubation. It was found that the apparent affinity of NHH analogs may be decreased ∼5 orders of magnitude with only minimal (20%) reduction in intrinsic activity. With further decrease in affinity to a critical Ka value, there was an abrupt decrease in intrinsic activity so that peptides with Ka ∼ 2 × 10-4M were either weak partial agonists or competitive antagonists. The tripeptide tails of NHH were not necessary for adenylate cyclase activation. No single amino acid in the ring moieties was essential for biol. activity. Receptor-mediated enzyme activation apparently involves the cooperative interaction of multiple elements of the ring with complementary elements of the receptor, with Asn5 and Tyr2 of the peptide ring playing critical roles. Studies of [Nε-acylated Lys8]vasopressin analogs have revealed it is possible to introduce carboxyl functions in the Lys8 side chain with unexpectedly high retention of affinity. Retro-D analogs of [Gly7]deaminooxytocin and deaminotocinamide, with a free NH2 group, were weak partial agonists; N-formylation, resulting in charge removal, led to loss of agonistic activity with development of antagonistic activity. Structural differences between the bovine and porcine renal receptor have previously been established with respect to position 8 of the vasopressin mol. A 2nd species difference, involving the NH2 terminus of the peptide was also found. The NH2 terminus increased binding affinity in the porcine receptor but not in the bovine receptor where deaminopressinamide [35748-54-0] had a higher affinity than pressinamide [27759-18-8], and 1-deaminooxytocin [113-78-0] had a higher affinity than oxytocin [50-56-6].
Journal of Biological Chemistry published new progress about Cell membrane. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Synthetic Route of 112-63-0.
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