AI Article Synopsis
- Developed mixed MOR/DOR agonists as enkephalin-like tetrapeptide analogs featuring a unique Ppp moiety at the C-terminus.
- Further studies led to the identification of a new multifunctional ligand, Dmt-DNle-Gly-Phe(-Cl)-Ppp, which shows both MOR/DOR agonist and KOR antagonist properties.
- This ligand demonstrates high binding affinity and therapeutic potential for managing chronic pain by balancing KOR activation with analgesic effects from its MOR/DOR activity.
Article Abstract
In our previous studies, we developed a series of mixed MOR/DOR agonists that are enkephalin-like tetrapeptide analogs with an N-phenyl-N-piperidin-4-ylpropionamide (Ppp) moiety at the C-terminus. Further SAR study on the analogs, initiated by the findings from off-target screening, resulted in the discovery of (, Dmt-DNle-Gly-Phe(-Cl)-Ppp), a multifunctional ligand with MOR/DOR agonist and KOR antagonist activity (GTPγS assay: IC = 52 nM, I = 122% cf. IC = 59 nM, I = 100% for naloxone) with nanomolar range of binding affinity ( = 1.3 nM cf. = 2.4 nM for salvinorin A). Based on its unique biological profile, is considered to possess high therapeutic potential for the treatment of chronic pain by modulating pathological KOR activation while retaining analgesic efficacy attributed to its MOR/DOR agonist activity.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229567 | PMC |
| http://dx.doi.org/10.3390/biomedicines9060625 | DOI Listing |
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