Objective: As a follow-up to our earlier studies on immunomodulation with opioid peptides, we synthesized and evaluated immunomodulatory activity of four peptidomimetic compounds, i.e. Tyr-NH-C(Me)2-CH2-O-Phe-NH2 (1), Tyr-NH-C6H5-(o)-CH2-CH2-O-Phe-NH2 (2), Tyr-NH-CH2-CH2-O-Phe-NH2 (3) and Tyr-NH-CH(D-Et)-CH2-O-Phe-NH2 (4). Methods: These compounds were synthesized in solution phase and evaluated for their immunomodulatory properties in vitro by mixed lymphocyte reaction (MLR), proliferation of opioid receptor-expressing cells, production of tumor necrosis factor-α (TNF-α) and nitric oxide. Results: This study shows the immunosuppressive potential of synthetic peptidomimetic compound 3. This compound inhibited two-way MLR and suppressed the proliferation of the µ-opioid receptor expressing human embryonic kidney cells HEK 293 in vitro. Inhibition of MLR by compound 3 was reversed by naloxone (opioid receptor antagonist) and β-funaltrexamine hydrochloride (µ-opioid receptor antagonist). The immunosuppressive effect of compound 3 was further demonstrated by inhibition of TNF-α and nitric oxide production in lipopolysaccharide-stimulated human PBMCs and mouse macrophage cells RAW 264.7, respectively. Conclusion: These observations suggest that compound 3 inhibits MLR through µ-opioid receptor present on cells.

Keywords:
Immunomodulator, Mixed lymphocyte reaction, Nitric oxide, Opioid peptide
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© 2001 S. Karger AG, Basel
2001
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