Rational approach to the design of bioactive peptidomimetics: Recent developments in opioid agonist peptides

Adriano Mollica, Azzurra Stefanucci, Roberto Costante, Victor J. Hruby

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations


Pharmacological management of severe and chronic pain remains a difficult achievement with currently available analgesic drugs. The design and development of potent opioid analogs with reduced tolerance, dependence, respiratory depression, and other unwanted side effects, could be of great value in the clinical treatment of chronic pain. The hierarchical approach to peptidomimetic design has dramatically advanced over the past three decades; a significant target in research since the discovery of multiple opioid receptors has been to develop highly potent and selective opioid receptor peptidomimetics that overcome the problems related to scarce bioavailability, enzymatic degradation, and low safety profile of natural peptides. Peptide drug design is a high multidisciplinary area that often relies on the state-of-the-art of organic chemistry, pharmacology, and biochemistry, computational methods and biophysical methods for determining the structural, conformational, topographical, and dynamic properties of designed ligands. With the aim to explore the recent advancements in opioids research, in this chapter, particular attention has been paid on the structural modifications of natural opioid peptides to obtain potent, selective, and stable opioid agonists. In addition, we focused our attention on μ/δ mixed agonists and novel approaches based on multitarget ligands, as discussed in section "Future Perspectives and Conclusions."

Original languageEnglish (US)
Title of host publicationStudies in Natural Products Chemistry
PublisherElsevier B.V.
Number of pages42
StatePublished - 2015

Publication series

NameStudies in Natural Products Chemistry
ISSN (Print)1572-5995


  • opioid receptor agonists antinociceptive profile peptidomimetics topographical constraints structure-activity relationship

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry


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