Lipid- and sugar-modified endomorphins: novel targets for the treatment of neuropathic pain

Endomorphins are endogenous opioid peptides that cause potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, endomorphins are poorly suited to clinical applications because of low membrane permeability and a susceptibility to enzymatic degradation. Glycosylation and lipidation have proven to be two of the most robust approaches for the generation of new therapeutic endomorphin derivatives. Conjugation with lipoamino acids (LAA) confers an amphipathic character to the peptide, which improved interaction between the peptide and the lipid bilayer of the cell membranes, increasing permeability. Glycosylation can also improve peptide stability and blood brain barrier (BBB) transport. It is believed that an endocytotic mechanism (transcytosis) is responsible for the systemic delivery of water-soluble glycopeptides. This review discusses the application of glycosylation and lipidation strategies to improve the drug-like properties of endomorphins. Pharmacologically active endomorphin analogs with less adverse effects are also discussed.

• Publication year

  2013

• Venue

  Frontiers in Pharmacology

• Publication date

  2013-12-13

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3389/fphar.2013.00155PMID 24379782PMCID 3862115
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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