Analogs of thyrotropin-releasing hormone using an aminoglycine-based template.
Novel thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2) analogs, made by 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 acylating agent derived from substituted (aromatic heterocyclic rings) formic or acetic acids or an aminotriazolyl moiety (3'-amino-1H-1',2',4'-triazolyl) built on N(alpha) of aminoglycine or Nbeta of alpha,beta-diaminoproprionic acid (Dpr). X was expected to mimic the electronic and structural characteristics of the imidazole ring of histidine. Analogs were purified by HPLC, characterized by mass spectrometry and isolated as either diastereoisomeric mixtures or pure isomers. Analogs, tested for their binding affinity to mouse pituitary TRH receptors, have apparent equilibrium inhibitory constants > 1 microM.
Kirby
D A
DA
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Wang
W
W
Gershengorn
M C
MC
Rivier
J E
JE
D000596:Amino Acids; D000818:Animals; D005998:Glycine / Q000031:analogs & derivatives*; D051379:Mice; D010902:Pituitary Gland / Q000737:chemistry; D011485:Protein Binding; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000378:metabolism; D013698:Templates, Genetic; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism
D000596:Amino Acids; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D005998:Glycine