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Updated: Mar 24, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs
Anna Adamska1, Alicja Kluczyk2, Maria Camilla Cerlesi3
1Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
Abstract:
Morphiceptin (Tyr-Pro-Phe-Pro-NH2), a tetrapeptide amide, is a selective ligand of the μ-opioid receptor (MOR). This study reports the synthesis and biological evaluation of a series of novel morphiceptin analogs modified in positions 2 or/and 4 by introduction of 4,4-difluoroproline (F2Pro) in l or d configuration. Depending on the fluorinated amino acid configuration and its position in the sequence, new analogs behaved as selective full MOR agonists showing high, moderate, or relatively low potency. The most potent analog, Tyr-F2Pro-Phe-D-F2Pro-NH2, was also able to activate the κ-opioid receptor (KOR), although with low potency. Docking studies and the comparison of results with the high resolution crystallographic structure of a MOR-agonist complex revealed possible structure-activity relationships of this compound family.
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