Abstract
Herein we present the expedient synthesis of endomorphin-1 analogues containing stereoisomeric β2-homo-Freidinger lactam-like scaffolds ([Amo2]EM), and we discuss opioid receptor (OR) affinity, enzymatic stability, functional activity, in vivo antinociceptive effects, and conformational and molecular docking analysis. Hence, H-Tyr-Amo-Trp-PheNH2 resulted to be a new chemotype of highly stable, selective, partial KOR agonist inducing analgesia, therefore displaying great potential interest as a painkiller possibly with reduced harmful side effects.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / chemical synthesis
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Analgesics / chemistry*
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Analgesics / metabolism
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Analgesics / pharmacology*
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Animals
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Dipeptides / chemistry*
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Heterocyclic Compounds / chemistry*
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Mice
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Molecular Docking Simulation
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry*
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Oligopeptides / metabolism
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Oligopeptides / pharmacology*
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Protein Conformation
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Receptors, Opioid, kappa / agonists*
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Receptors, Opioid, kappa / chemistry
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Receptors, Opioid, kappa / metabolism
Substances
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Analgesics
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Dipeptides
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Heterocyclic Compounds
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Oligopeptides
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Receptors, Opioid, kappa
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endomorphin 1