Tritium-markierte reaktive Analoga des [1,6-α-Aminosuberinsäure, 8-Arginin]Vasopressins (Desamino-dicarba-[8-Arginin]vasopressin). Synthese und Eigenschaften

Abstract

The synthesis of 3 reactive analogs of [1,6-.alpha.-aminosuberic acid, 8-arginine]-vasopressin ([Asu1,6, Arg8]vasopressin) is described. Two peptide hormone analogs contain in the p-position of Phe2 the azido or 3-(3-methyl-3-diazirinyl)propanoylamino residue, which can be converted by photoactivation into nitrenes and carbenes, respectively. The 3rd derivative contains the chemically reactive (bromoacetyl)amino group in the same position. The analogs are prepared via the precursor [Asu1,6, Phe(pNH2)2, Arg8]vasopressin, which is obtained by peptide synthesis in solution. Modifications of the p-amino group of Phe(pNH2) give the reactive analogs. The analog containing p-azidophenylalanine in position 2 show a similar high binding affinity for the antidiuretic receptor in bovine kidney as vasopressin. By iodination of the Phe(pNH2) residue, followed by catalytic dehalogenation, the 2-(p-aminophenylalanine) analog is labeled with tritium at a specific radioactivity of 16 Ci/mmol. It can be converted into the tritium-labeled 2-(p-azidophenylalanine) analog without loss of binding affinity for vasopressin receptors.