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Review
. 2022 Sep 5;12(9):1241.
doi: 10.3390/biom12091241.

Peptidomimetics and Their Applications for Opioid Peptide Drug Discovery

Yeon Sun Lee  1
Affiliations
Review

Peptidomimetics and Their Applications for Opioid Peptide Drug Discovery

Yeon Sun Lee. Biomolecules. .

Abstract

Despite various advantages, opioid peptides have been limited in their therapeutic uses due to the main drawbacks in metabolic stability, blood-brain barrier permeability, and bioavailability. Therefore, extensive studies have focused on overcoming the problems and optimizing the therapeutic potential. Currently, numerous peptide-based drugs are being marketed thanks to new synthetic strategies for optimizing metabolism and alternative routes of administration. This tutorial review briefly introduces the history and role of natural opioid peptides and highlights the key findings on their structure-activity relationships for the opioid receptors. It discusses details on opioid peptidomimetics applied to develop therapeutic candidates for the treatment of pain from the pharmacological and structural points of view. The main focus is the current status of various mimetic tools and the successful applications summarized in tables and figures.

Keywords: analgesic drugs; bioavailability; locally constrained peptides; opioid receptors; peptide backbone modifications; peptidomimetic.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 5
Figure 5
Structures of selective opioid peptidomimetic.
Figure 1
Figure 1
Subtype selective opioid peptidomimetics developed from endogenous opioid peptides.
Figure 2
Figure 2
Various modifications to optimize metabolic stability, BBB permeability, and oral bioavailability.
Figure 3
Figure 3
Multifunctional opioid peptidomimetics: MOR/DOR agonist, MOR agonist/DOR antagonist.
Figure 4
Figure 4
Message and address regions of natural opioid peptides.
Figure 6
Figure 6
Various tools for peptidomimetics.
Figure 7
Figure 7
Structures of β-amino acids (upper) and alicyclic β-amino acids (lower). * Chiral.
Figure 8
Figure 8
Structures of constrained amino acids and dipeptidic scaffolds. * Chiral.
Figure 9
Figure 9
Cβ-substituted amino acids. * Chiral.
Figure 10
Figure 10
Structures of Leucine derivatives.
See this image and copyright information in PMC

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References

    1. Farmer P., Ariens E. Speculations on the design of nonpeptidic peptidomimetics. Trends Pharmacol. Sci. 1982;3:362–365. doi: 10.1016/0165-6147(82)91184-1. - DOI
    1. Wang L., Wang N., Zhang W., Cheng X., Yan Z., Shao G., Wang X., Wang R., Fu C. Therapeutic peptides: Current applications and future directions. Sign. Trans. Targeted Therap. 2022;7:1–27. - PMC - PubMed
    1. Eguchi M. Recent advances in selective opioid receptor agonists and antagonists. Med. Res. Rev. 2004;24:182–212. - PubMed
    1. Onogi T., Minami M., Katao Y., Nakagawa T., Aoki Y., Toya T., Katsumata S., Satoh M. DAMGO, a μ-opioid receptor selective agonist, distinguishes between μ-and δ-opioid receptors around their first extracellular loops. FEBS Lett. 1995;357:93–97. doi: 10.1016/0014-5793(94)01341-W. - DOI - PubMed
    1. Johnson K.V.-A., Dunbar R.I. Pain tolerance predicts human social network size. Sci. Rep. 2016;6:1–5. - PMC - PubMed

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