Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Delta(3)Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (DeltaAla) have been used to prepare [Delta(3)Pro(2)]EM-2 (1), [Aze(2)]EM-1 (2), [Aze(2)]EM-2 (3), [3Aze(2)]EM-1 (4), [3Aze(2)]EM-2 (5) and [DeltaAla(2)]EM-2 (6). Binding assays and functional bioactivities for mu- and delta-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737817 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2009.06.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cyclic Glycopeptide Analogs of Endomorphin-1 Provide Highly Effective Antinociception in Male and Female Mice.
ACS Med Chem Lett
October 2024
Department of Chemistry & Biochemistry, The University of Arizona, Tucson, Arizona 85721, United States.
Article Synopsis
- Opioids, particularly those targeting the mu opioid receptor (MOR), are effective for severe pain but have serious side effects that limit their use.
- Researchers developed cyclic glycopeptide endomorphin (glycoEM) analogs that provided pain relief similar to morphine while reducing side effects, including lower abuse potential.
- In studies with male and female mice, two glycoEM analogs exhibited higher potency and longer-lasting pain relief at much lower doses than morphine, suggesting potential for future clinical applications.
Comparison of Morphine and Endomorphin Analog ZH853 for Tolerance and Immunomodulation in a Rat Model of Neuropathic Pain.
J Pain
October 2024
Neuroscience Program/Brain Institute, Tulane University School of Medicine, New Orleans, Louisiana; SE LA Veterans Health Care System, Tulane University School of Medicine, New Orleans, Louisiana; Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana; Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address:
µ-Opioid receptor agonists, the gold standard for analgesia, come with significant side effects when used chronically. Tolerance, defined as the decrease in analgesic activity after repeated use, remains a vital therapeutic obstacle as it increases the likelihood of dose escalation and potentially lethal side effects like respiratory depression. Previous experiments have shown that the endomorphin-1 analog, ZH853, is a specific µ-opioid receptor agonist with reduced side effects like tolerance and glial activation following chronic central administration in pain-naive animals.
View Article and Find Full Text PDFNovel Opioids in the Setting of Acute Postoperative Pain: A Narrative Review.
Pharmaceuticals (Basel)
December 2023
Department of Anesthesiology, Stony Brook University Hospital, Stony Brook, NY 11794, USA.
Although traditional opioids such as morphine and oxycodone are commonly used in the management of acute postoperative pain, novel opioids may play a role as alternatives that provide potent pain relief while minimizing adverse effects. In this review, we discuss the mechanisms of action, findings from preclinical studies and clinical trials, and potential advantages of several novel opioids. The more established include oliceridine (biased ligand activity to activate analgesia and downregulate opioid-related adverse events), tapentadol (mu-opioid agonist and norepinephrine reuptake inhibitor), and cebranopadol (mu-opioid agonist with nociceptin opioid peptide activity)-all of which have demonstrated success in the clinical setting when compared to traditional opioids.
View Article and Find Full Text PDFNovel endomorphin analogues CEMR-1 and CEMR-2 produce potent and long-lasting antinociception with a favourable side effect profile at the spinal level.
Br J Pharmacol
April 2024
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Background And Purpose: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent μ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.
View Article and Find Full Text PDFEndomorphin-2 analogs with C-terminal esterification display potent antinociceptive effects in the formalin pain test in mice.
Peptides
January 2024
School of Life Science and Technology, Harbin Institute of Technology, 92 West Dazhi Street, Harbin 150001, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, China. Electronic address:
Previously, we have investigated three C-terminal esterified endomorphin-2 (EM-2) analogs EM-2-Me, EM-2-Et and EM-2-Bu with methyl, ethyl and tert-butyl ester modifications, respectively. These analogs produced significant antinociception in acute pain at the spinal and supraspinal levels, with reduced tolerance and gastrointestinal side effects. The present study was undertaken to determine the analgesic effects and opioid mechanisms of these three analogs in the formalin pain test.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!