Brain-targeted chemical delivery of [Leu 2 , Pip 3 ]-TRH
| Autor: | Jiaxiang Wu, Whei-Mei Wu, Laszlo Prokai, Nicholas Bodor, Sung-Hwa Yoon |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
chemistry.chemical_classification
endocrine system Organic Chemistry Clinical Biochemistry Pharmaceutical Science Biological activity Peptide Blood–brain barrier Biochemistry Chemical synthesis Pentapeptide repeat chemistry.chemical_compound medicine.anatomical_structure chemistry Prolyl endopeptidase Drug Discovery medicine Peptide synthesis Molecular Medicine Drug carrier Molecular Biology medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 8:1059-1063 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(00)00043-2 |
| Popis: | A chemical targeting system for [Leu 2 , Pip 3 ]-TRH (Gln,Leu,Pip) was synthesized in order to allow its specific delivery to the central nervous system (CNS). Sequential metabolism of the obtained ‘packaged’ chemical delivery system, (CDS), DHT-Pro-Pro-Gln-Leu-Pip-OCh, should yield a ‘locked-in’ precursor following the oxidative conversion of the dihydrotrigonellyl (DHT) to the trigonellyl (T + ) moiety, followed by removal of the cholesteryl function and cleavage of the T + -Pro-Pro by prolyl endopeptidase. The antagonism of barbiturate-induced sleeping time was used to assess the activity of the CDS. The sleeping time after administration of vehicle and [Leu 2 ]-TRH was 100.5±6.3 min, and 78.2±4.7 min, respectively. The [Leu 2 , Pip 3 ]-TRH-CDS showed a significant decrease in sleeping time (58.2±3.4 min) compared to the vehicle or [Leu 2 ]-TRH. These results indicate successful brain delivery of the precursor construct, and an effective release of the active GlnLeuPip in the brain. |
| Databáze: | OpenAIRE |
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