Bioorganic & Medicinal Chemistry Letters 2003-03-24

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

Index: Bioorg. Med. Chem. Lett. 13(6) , 1011-4, (2003)

Full Text: HTML

Abstract

Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH(2) 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-NH(2) with long-chain primary alcohols emerged as potentially useful prodrugs to improve the central nervous system activity of pGlu-Glu-Pro-NH(2) upon systemic administration, as revealed by the enhancement of analeptic activity in mice.


Related Compounds

  • [Glu2]-TRH

Related Articles:

Fertilization promoting peptide--a possible regulator of sperm function in vivo.

2001-01-01

[Vitam. Horm. 63 , 1-28, (2001)]

Fertilization promoting peptide and adenosine, acting as first messengers, regulate cAMP production and consequent protein tyrosine phosphorylation in a capacitation-dependent manner.

2000-12-01

[Mol. Reprod. Dev. 57(4) , 384-92, (2000)]

In vitro neuroprotection against glutamate-induced toxicity by pGlu-Glu-Pro-NH(2) (EEP).

2001-12-01

[Peptides 22(12) , 2091-7, (2001)]

Molecular characterization of the TCP11 gene which is the human homologue of the mouse gene encoding the receptor of fertilization promoting peptide.

2002-01-01

[Mol. Hum. Reprod. 8(1) , 24-31, (2002)]

Substrate specificity of glutaminyl cyclases from plants and animals.

2003-12-01

[Biol. Chem. 384(12) , 1583-92, (2003)]

More Articles...