Analogs of thyrotropin-releasing hormone using an aminoglycine-based template

Novel thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2) analogs, made b y solid phase, were derived from the general scaffold pGlu-(D/L)Agl(X)-Pro- NH2 where Agl = aminoglycine. Analogs ranged from X being a proton to an ac ylating agent derived from substituted (aromatic heterocyclic rings) formic or acetic acids or an aminotriazolyl moiety (3'-amino-1H-1',2',4'-triazoly l) built on N-alpha of aminoglycine or N-beta of alpha,beta-diaminoproprion ic acid (Dpr). X was expected to mimic the electronic and structural charac teristics of the imidazole ring of histidine. Analogs were purified by HPLC , characterized by mass spectrometry and isolated as either diastereoisomer ic mixtures or pure isomers. Analogs, tested for their binding affinity to mouse pituitary TRH receptors, have apparent equilibrium inhibitory constan ts >1 mu M. (C) 1998 Elsevier Science Inc.