Synthesis of the phosphinic analogue of thyrotropin releasing hormone |
| |
Authors: | Matziari Magdalini Bauer Karl Dive Vincent Yiotakis Athanasios |
| |
Institution: | Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece. |
| |
Abstract: | The synthesis of the phosphinic analogue of thyrotropin releasing hormone (TRH) GlpPsiP(O)(OH)]HisProNH2, where the scissile peptide bond of TRH has been replaced by the hydrolytically stable phosphinic bond, has been achieved by a multistep synthetic strategy, providing thus one of the most potent synthetic inhibitors of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)PsiP(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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|