Prodrugs to enhance central nervous system effects of the TRH-like peptide pGlu-Glu-Pro-NH2

Katalin Prokai-Tatrai, Vien Nguyen, Alevtina D. Zharikova, April C. Braddy, Stanley M. Stevens, Laszlo Prokai

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH2 were synthesized either by esterifying the Glu side-chain of the parent peptide in solution with alcohols in the presence of resin-bound dicyclohexylcarbodiimide or by solid-phase peptide chemistry. Affinities of these ester prodrugs to lipid membranes as predictors of the transport across the blood-brain barrier were compared by immobilized artificial membrane chromatography, and prodrug activation was tested in the brain tissue of experimental animals. Esters of pGlu-Glu-Pro-NH2 with long-chain primary alcohols emerged as potentially useful prodrugs to improve the central nervous system activity of pGlu-Glu-Pro-NH2 upon systemic administration, as revealed by the enhancement of analeptic activity in mice.

Original languageEnglish
Pages (from-to)1011-1014
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number6
DOIs
StatePublished - 24 Mar 2003

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