Glycopeptide analgesics

Robin L Polt, M. M. Palian

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Excluding insulin, the global market for peptide pharmaceuticals is expected to grow from $350 million in 1999 to over $800 million by 2005 (1). Despite their advantages of potency, specificity and low toxicity, peptides have not gained the rapid acceptance by the pharmaceutical industry that one might have predicted in the 1970s, chiefly due to difficulties in peptide manufacture and poor bioavailability. Results from several studies now demonstrate that O-linked glycosylation of peptides can promote the serum stability of several classes of peptides in vivo, and can promote the transport of enkephalin analogs across the blood-brain barrier (BBB). Recent work with glycosylated enkephalin analogs suggests that the incorporation of a glycosylated serine or threonine residue promotes transport across the BBB, which resulted in an AUC increase of over 30-fold in rats. Antinociception assays with mice demonstrate that glycosylated enkephalins can compete with morphine in efficacy, even when administered peripherally. Proper placement of the glycoside moiety is necessary in order to avoid perturbation of the mu/delta selectivity of the parent peptide pharmacophore.

Original languageEnglish (US)
Pages (from-to)561-576
Number of pages16
JournalDrugs of the Future
Volume26
Issue number6
DOIs
StatePublished - 2001

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Glycopeptides
Analgesics
Peptides
Enkephalins
Blood-Brain Barrier
Drug Industry
Threonine
Glycosides
Glycosylation
Serine
Morphine
Biological Availability
Area Under Curve
Insulin
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Pharmacology

Cite this

Glycopeptide analgesics. / Polt, Robin L; Palian, M. M.

In: Drugs of the Future, Vol. 26, No. 6, 2001, p. 561-576.

Research output: Contribution to journalArticle

Polt, Robin L ; Palian, M. M. / Glycopeptide analgesics. In: Drugs of the Future. 2001 ; Vol. 26, No. 6. pp. 561-576.
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