title: Synthesis of the phosphinic analogue of thyrotropin releasing hormone.
abstract: The synthesis of the phosphinic analogue of thyrotropin releasing hormone (TRH) GlpPsi[P(O)(OH)]HisProNH2, where the scissile peptide bond of TRH has been replaced by the hydrolytically stable phosphinic bond, has been achieved by a multistep synthetic strategy, providing thus one of the most potent synthetic inhibitors of pyroglutamyl peptidase II (PPII) reported to date (170 nM). The key synthetic step, an Ugi-type condensation reaction, produced directly the suitably protected for solid-phase peptide synthesis pseudodipeptidic block FmocGlu(OMe)Psi[P(O)(OH)]His(Tr)OH. Formation of the pyroglutamic ring was performed on solid phase, providing thus a general method for synthesizing pyroglutamyl phosphinic peptides on solid phase. Using this strategy, the phosphinic analogue of TRH has been synthesized for the first time.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Matziari
authors.forename: Karl
authors.initials: K
authors.lastname: Bauer
authors.forename: Vincent
authors.initials: V
authors.lastname: Dive
authors.forename: Athanasios
authors.initials: A
authors.lastname: Yiotakis
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D010721:Phosphinic Acids / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D010721:Phosphinic Acids; D011480:Protease Inhibitors; D013973:Thyrotropin-Releasing Hormone; D000626:Aminopeptidases; C023166:pyroglutamyl-peptidase II; D011761:Pyrrolidonecarboxylic Acid