Enkephalin glycopeptide analogues produce analgesia with reduced dependence liability

Edward J. Bilsky, Richard D. Egleton, Scott A. Mitchell, Michael M. Palian, Peg Davis, Jason D. Huber, Heather Jones, Henry I. Yamamura, Jacqueline Janders, Thomas P. Davis, Frank Porreca, Victor J. Hruby, Robin Polt

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Endogenous peptides (e.g. enkephalins) control many aspects of brain function, cognition, and perception. The use of these neuroactive peptides in diverse studies has led to an increased understanding of brain function. Unfortunately, the use of brain-derived peptides as pharmaceutical agents to alter brain chemistry in vivo has lagged because peptides do not readily penetrate the blood-brain barrier. Attachment of simple sugars to enkephalins increases their penetration of the blood-brain barrier and allows the resulting glycopeptide analogues to function effectively as drugs. The δ- selective glycosylated Leu-enkephalin amide 2, H2N-TyrD-Thr-Gly-Phe-Leu- Ser(β-D-Glc)-CONH2, produces analgesic effects similar to morphine, even when administered peripherally, yet possesses reduced dependence liability as indicated by naloxone-precipitated withdrawal studies. Similar glycopeptide- based pharmaceuticals hold forth the promise of pain relief with improved side-effect profiles over currently available opioid analgesics.

Original languageEnglish (US)
Pages (from-to)2586-2590
Number of pages5
JournalJournal of Medicinal Chemistry
Issue number13
StatePublished - Jun 29 2000

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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