Peptides (New York, N.Y. : 1980), 2014-05, Vol.55, p.145-150
2014
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- Autor(en) / Beteiligte
- Titel
- Pharmacological characterization of endomorphin-2-based cyclic pentapeptides with methylated phenylalanine residues
- Ist Teil von
- Peptides (New York, N.Y. : 1980), 2014-05, Vol.55, p.145-150
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- •A new series of cyclic endomorfin-2-based analogs was synthesized.•Calcium mobilization assay was used in functional studies.•Extraordinary MOP and KOP receptor activities were achieved.•Strong antinociceptive activity in mice was observed. As part of our continuing studies on the structure–activity relationships of cyclic pentapeptides based on the structure of endomorphin-2, we report here the synthesis and biological activities of a new series of analogs incorporating 2′, 3′ or 4′-methylphenylalanine (MePhe) residues into positions 3 or 4 of the parent cyclopeptide, Dmt-c[d-Lys-Phe-Phe-Asp]NH2 (Dmt=2′,6′-dimethyltyrosine). Analogs with MePhe in position 4 showed a row of magnitude increased μ-opioid receptor (MOP receptor) affinity as compared with a parent compound. The in vitro potencies of the new analogs were determined in calcium mobilization assay performed in Chinese Hamster Ovary (CHO) cells expressing human recombinant opioid receptors and chimeric G proteins. All analogs were strong μ/κ (MOP/KOP) receptor agonists and weak δ (DOP) receptor agonists. In the in vivo hot-plate test in mice, the MePhe4-modified peptides showed remarkable antinociceptive activity after intracerebroventricular (i.c.v.) administration which was most likely due to the concomitant activation of more than one opioid receptor type.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0196-9781eISSN: 1873-5169DOI: 10.1016/j.peptides.2014.03.001Titel-ID: cdi_proquest_miscellaneous_1762141912
- Format
- –
- Schlagworte
- Activation, Analgesics, Opioid - administration & dosage, Analgesics, Opioid - chemistry, Analogs, Animals, Calcium mobilization, CHO Cells, Cricetinae, Cricetulus, Cyclic peptides, Drug Evaluation, Preclinical, Hot-plate test, Humans, Inhibitory Concentration 50, Injections, Intraventricular, Male, Mice, Oligopeptides - administration & dosage, Oligopeptides - chemistry, Opioid receptors, Parents, Peptides, Phenylalanine - analogs & derivatives, Phenylalanine - chemistry, Protein Binding, Rats, Wistar, Receptor binding, Receptors, Receptors, Opioid, delta - agonists, Receptors, Opioid, delta - metabolism, Receptors, Opioid, mu - agonists, Receptors, Opioid, mu - metabolism, Recombinant, Residues, Solid phase peptide synthesis, Structure-Activity Relationship