Synthesis of the phosphinic analogue of thyrotropin releasing hormone.
J Org Chem
; 73(21): 8591-3, 2008 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-18826326
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analogue of thyrotropin releasing hormone (TRH) GlpPsi[P(O)(OH)]HisProNH2, where the scissile peptide bond of TRH has been replaced by the hydrolytically stable phosphinic bond, has been achieved by a multistep synthetic strategy, providing thus one of the most potent synthetic inhibitors of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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Fosfínicos
/
Ácido Pirrolidonocarboxílico
/
Hormônio Liberador de Tireotropina
/
Aminopeptidases
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Grécia