A strategy for delivering peptides into the central nervous system by sequential metabolism

Nicholas Bodor, Laszlo Prokai, Wei Mei Wu, Hassan Farag, Sastry Jonalagadda, Masanori Kawamura, James Simpkins

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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.

Original languageEnglish
Pages (from-to)1698-1700
Number of pages3
JournalScience
Volume257
Issue number5077
DOIs
StatePublished - 1 Jan 1992

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    Bodor, N., Prokai, L., Wu, W. M., Farag, H., Jonalagadda, S., Kawamura, M., & Simpkins, J. (1992). A strategy for delivering peptides into the central nervous system by sequential metabolism. Science, 257(5077), 1698-1700. https://doi.org/10.1126/science.1529356