Matziari Magdalini, Bauer Karl, Dive Vincent, Yiotakis Athanasios
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
J Org Chem. 2008 Nov 7;73(21):8591-3. doi: 10.1021/jo8014215. Epub 2008 Oct 1.
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analogue of thyrotropin releasing hormone (TRH) GlpPsi[P(O)(OH)]HisProNH2, where the scissile peptide bond of TRH has been replaced by the hydrolytically stable phosphinic bond, has been achieved by a multistep synthetic strategy, providing thus one of the most potent synthetic inhibitors of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.
