Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration
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Tartalom: http://real.mtak.hu/49903/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration
Létrehozó:
Perlikowska, Renata
Piekielna, Justyna
Gentilucci, Luca
De Marco, Rossella
Cerlesi, Maria Camilla
Tömböly, Csaba
Kiadó:
Elsevier
Dátum:
2016
Téma:
QH3011 Biochemistry / biokémia
QH3015 Molecular biology / molekuláris biológia
Tartalmi leírás:
Cyclic pentapeptide Tyr-c[D-Lys-Phe-Phe-Asp]NH2, based on the structure of endomorphin-2 (EM-2), which shows high affinity to the μ-opioid receptor (MOR) and a very strong antinociceptive activity in mice was used as a parent compound for the structure-activity relationship studies. In this report we synthesized analogs of a general sequence Dmt-c[D-Lys-Xaa-Yaa-Asp]NH2, with D-1- or D-2-naphthyl-3-alanine (D-1-Nal or D-2-Nal) in positions 3 or 4. In our earlier papers we have indicated that replacing a phenylalanine residue by the more extended aromatic system of naphthylalanines may result in increased bioactivities of linear analogs. The data obtained here showed that only cyclopeptides modified in position 4 retained the sub-nanomolar MOR and nanomolar κ-opioid receptor (KOR) affinity, similar but not better than that of a parent cyclopeptide. In the in vivo mouse hot-plate test, the most potent analog, Dmt-c[D-Lys-Phe-D-1-Nal-Asp]NH2, exhibited higher than EM-2 but slightly lower than the cyclic parent peptide antinociceptive activity after peripheral (ip) and also central administration (icv). Conformational analyses in a biomimetic environment and molecular docking studies disclosed the structural determinants responsible for the different pharmacological profiles of position 3- versus position 4-modified analogs. © 2015 Published by Elsevier Masson SAS.
Nyelv:
angol
Típus:
Article
PeerReviewed
info:eu-repo/semantics/article
Formátum:
text
Azonosító:
Perlikowska, Renata and Piekielna, Justyna and Gentilucci, Luca and De Marco, Rossella and Cerlesi, Maria Camilla and Tömböly, Csaba (2016) Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 109. pp. 276-286. ISSN 0223-5234
Kapcsolat:
MTMT:3028049; doi:10.1016/j.ejmech.2015.12.012