Design, Synthesis and Pharmacological Characterization of Endomorphin Analogues with Non-Cyclic Amino Acid Residues in Position 2. Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] Journal article | | Title | Design, Synthesis and Pharmacological Characterization of Endomorphin Analogues with Non-Cyclic Amino Acid Residues in Position 2. | | Author(s) | Perlikowska R, Fichna J, Wyrębska A, Poels J, Vanden Broeck J, Toth G, Storr M, do Rego JC, Janecka A | | Institution | Department of Biomolecular Chemistry, Medical University, Lodz, Poland. | | Source | Basic Clin Pharmacol Toxicol 2009 Oct 28. | | Abstract | A series of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) analogues, containing non-cyclic amino acids (Ala, d-Ala, beta-Ala, NMeAla, d-NMeAla or Sar) instead of Pro in position 2 was synthesized, where NMeAla = N-methylalanine and Sar = N-methylglycine, sarcosine. The opioid activity profiles of these peptides were determined in mu and delta opioid receptor (MOR and DOR)-representative binding assays and bioassays in vitro, as well as in the mouse hot-plate test in vivo. Finally, the degradation rates of all analogues in the presence of either rat brain homogenate or selected proteolytic enzymes were determined. Analogues of EM-2 were generally more potent than the respective analogues of EM-1. EM-2 analogues with d-Ala or d-NMeAla were about twofold more potent than the parent peptide and were least prone to degradation by brain homogenate, dipeptydyl peptidase IV and aminopeptidase M. In the in vivo test, [d-Ala(2)]EM-2 and [d-NMeAla(2)]EM-2 showed much higher analgesic potency than EM-2 which confirmed the usefulness of structural modifications in obtaining new leads for pain-relief therapeutics. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19874287 |
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