New prospects for glycopeptide based analgesia: Glycoside-induced penetration of the Blood-Brain Barrier

Muthu Dhanasekaran, Robin Polt

Research output: Contribution to journalReview article

26 Scopus citations

Abstract

Antinociceptive effects and BBB transport properties of glycosylated enkephalin derivatives are reviewed. Previously, the application of enkephalins as analgesics has been retarded by their poor stability in vivo and by their inability to effectively penetrate the blood brain barrier. This shortcoming has been overcome by glycosylation, paradoxically leading to enhanced BBB transport via transcytosis. Principal design considerations required for enhanced binding, stability and transport of opioid peptides are reviewed. Modifications of the peptide backbone and side chains to achieve optimal receptor binding (μ/δ-selectivity) are presented. The importance of reversible binding between the glycopeptide and membranes is emphasized, and several pertinent examples of peptide-membrane interactions are discussed in the light of glycopeptide transport and opioid binding. An "amphipathic hypothesis" is introduced as a rationale for the observed BBB penetration of the opioid glycopeptides.

Original languageEnglish (US)
Pages (from-to)59-73
Number of pages15
JournalCurrent Drug Delivery
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • Analgesia
  • Blood-Brain Barrier
  • Enkephalin
  • Glycopeptide
  • Morphine
  • Opioid
  • Transcytosis

ASJC Scopus subject areas

  • Pharmaceutical Science

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