Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 18 September 1992:
Vol. 257. no. 5077, pp. 1698 - 1700
DOI: 10.1126/science.1529356
Prev | Table of Contents | Next

Articles

Science, Vol 257, Issue 5077, 1698-1700
Copyright © 1992 by American Association for the Advancement of Science

articles

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

N Bodor, L Prokai, WM Wu, H Farag, S Jonalagadda, M Kawamura, and J Simpkins

Center for Drug Discovery, College of Pharmacy, J. Hillis Miller Health Center, University of Florida, Gainesville 32610.

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Antinociceptive Structure-Activity Studies with Enkephalin-Based Opioid Glycopeptides.
N. O. Elmagbari, R. D. Egleton, M. M. Palian, J. J. Lowery, W. R. Schmid, P. Davis, E. Navratilova, M. Dhanasekaran, C. M. Keyari, H. I. Yamamura, et al. (2004)
J. Pharmacol. Exp. Ther. 311, 290-297
   Abstract »    Full Text »    PDF »
Structure-Activity Relationships of a Series of [D-Ala2]Deltorphin I and II Analogues; in Vitro Blood-Brain Barrier Permeability and Stability.
S. A. Thomas, T. J. Abbruscato, V. S. Hau, T. J. Gillespie, J. Zsigo, V. J. Hruby, and T. P. Davis (1997)
J. Pharmacol. Exp. Ther. 281, 817-825
   Abstract »    Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)