Wydział Chemii

Katarzyna Gach-Janczak

Justyna Piekielna-Ciesielska

Anna Adamska-Bartłomiejczyk

Renata Perlikowska

Rafał Kruszyński

Alicja Kluczyk

Julia Krzywik

Jarosław Sukiennik

Maria Camilla Cerlesi

Girolamo Calò

Andrzej Wasilewski

Marta Zielińska

Anna Janecka

2017

Peptides

95

116-123

10.1016/j.peptides.2017.07.015

Naukowa

Angielski

Artykuł

Morphiceptin (Tyr-Pro-Phe-Pro-NH₂) is a selective ligand of the mu opioid receptor, an important target in pain regulation. In this study, morphiceptin was modified at positions 2 or 3 by introduction of β²- or β³-amino acids and additionally in position 1 by replacing Tyr by Dmt (2',6'-dimethyltyrosine), which resulted in obtaining enzymatically stable analogs with mixed opioid receptor affinity profiles. An analog of the sequence Dmt-d-Ala-(R)-β²-1-Nal-Pro-NH₂ [Nal=3-(1-naphthyl)-alanine] showed very high activity at the mu and delta receptors in the calcium mobilization functional test but did not cross the artificial membrane imitating the blood-brain barrier. In the in vivo test this analog induced strong antinociceptive effect in the writhing test in mice after intraperitioneal but also oral administration and inhibited diarrhea similarly to loperamide. Therefore, it may become an interesting lead compound in the development of peripherally restricted drugs for the treatment of gastrointestinal disorders.

Binding assay, calcium mobilization assay, Enzymatic degradation, Peptide synthesis, Writhing test, β-amino acids

http://dx.doi.org/10.1016/j.peptides.2017.07.015

http://www.elsevier.com