Wydział Chemii

Renata Perlikowska

Davide Malfacini

Maria Camilla Cerlesi

Girolamo Calò

Justyna Piekielna

Léonore Floriot

Tiphaine Henry

Jean Claude do-Rego

Csaba Tömböly

Alicja Kluczyk

Anna Janecka

2014

Peptides

55

145-150

10.1016/j.peptides.2014.03.001

Naukowa

Angielski

Artykuł

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.

Solid phase peptide synthesis, Cyclic peptides, Opioid receptors, Receptor binding, Calcium mobilization, Hot-plate test

http://dx.doi.org/10.1016/j.peptides.2014.03.001

http://www.elsevier.com