Repozytorium
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Kolekcje
Inne
Endomorphin-2 analogs containing modified tyrosines: Biological and theoretical investigation of the influence on conformation and pharmacological profile.
Autorzy
Rok wydania
2019
Czasopismo
European Journal of Medicinal Chemistry
Numer woluminu
179
Strony
527-536
DOI
10.1016/j.ejmech.2019.06.077
Kolekcja
Język
Angielski
Typ publikacji
Artykuł
New analogs of the endogenous opioid agonist endomorphin-2 (EM-2, H-Tyr-Pro-Phe-Phe-NH2) have been obtained by introducing modified tyrosines at the position 1 of the sequence. For all analogs, the cis/trans conformation ratio about the tyramine-Pro amide bond, lipophilicity, receptor affinities, and functional activities, have been determined. Among the novel derivatives, [Dmt(3′-Cl)]1EM-2 (4) stood out for its subnanomolar μ-opioid receptor affinity and potent agonist activity, superior to that of the parent peptide EM-2. Hybrid quantum mechanics/molecular mechanics docking computations supported the cis tyramine-Pro bioactive conformation, and allowed us to analyze the contribution of the substituents of the “message” tyramine to binding, highlighting the role of halogen-bonding in the higher receptor affinity of peptide 4.
Słowa kluczowe
Opioid peptides, Tyrosine analogs, Molecular docking, Halogen-bond
Adres publiczny
http://dx.doi.org/10.1016/j.ejmech.2019.06.077
Strona internetowa wydawcy
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