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In vitro Characterization of Novel Peptide Inhibitors of Endomorphin‐degrading Enzymes in the Rat Brain
Author(s) -
Fichna Jakub,
Janecka Anna,
Bailly Laetitia,
Marsais Francis,
Costentin Jean,
Rego JeanClaude do
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00425.x
Subject(s) - tripeptide , chemistry , receptor , peptide , enzyme , endogeny , biochemistry , in vivo , in vitro , pharmacology , opioid peptide , opioid , biology , microbiology and biotechnology
Endomorphins, endogenous μ ‐opioid receptor ligands, have been shown to exert antinociceptive, antidepressant, anxiolytic, and neuromodulatory effects, as well as to influence cardiovascular, respiratory, and gastrointestinal systems. In the present study, we designed and synthesized a series of tetrapeptides and tripeptides (amides and peptide acids) of similar to endomorphins structure, but with low μ ‐opioid receptor affinity, and tested them as possible inhibitors of endomorphin‐degrading enzymes. The obtained results indicate that the tripeptides Tyr‐Pro‐Ala‐NH 2 and Tyr‐Pro‐Ala‐OH, which do not bind to the μ ‐opioid receptors, are potent inhibitors of endomorphin‐degrading enzymes in the rat brain. We suggest that the in vivo administration of these novel analogs may enhance physiological effects of endogenous endomorphins by decreasing the rate of their enzymatic cleavage.