A strategy for delivering peptides into the central nervous system by sequential metabolism.
Science
; 257(5077): 1698-700, 1992 Sep 18.
Article
em En
| MEDLINE
| ID: mdl-1529356
ABSTRACT
Most peptides do not enter the central nervous system because of their hydrophilic character and the presence of peptidolytic enzymes in the lipoidal blood-brain barrier. To achieve brain delivery of a peptide conjugate, an opioid peptide (enkephalin) was placed in a molecular environment that disguises its peptide nature and provides biolabile, lipophilic functions to penetrate the blood-brain barrier by passive transport. The strategy also incorporates a 1,4-dihydrotrigonellinate targetor that undergoes an enzymatically mediated oxidation to a hydrophilic, membrane-impermeable trigonellinate salt. The polar targetorpeptide conjugate that is trapped behind the lipoidal blood-brain barrier is deposited in the central nervous system. Analgesia was observed with "packaged" enkephalin but not with the unmodified peptide or lipophilic peptide precursors.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Encéfalo
/
Pró-Fármacos
/
Barreira Hematoencefálica
Limite:
Animals
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article