Repozytorium

Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues.

Autorzy

Anna Adamska-Bartłomiejczyk

Anna Janecka

Márton Richárd Szabó

Maria Camilla Cerlesi

Girolamo Calò

Alicja Kluczyk

Csaba Tömböly

Attila Borics

Rok wydania

2017

Czasopismo

Bioorganic and Medicinal Chemistry Letters

Numer woluminu

27

Strony

1644-1648

DOI

10.1016/j.bmcl.2017.03.016

Kolekcja

Naukowa

Język

Angielski

Typ publikacji

Artykuł

Streszczenie

In this study we report the in vitro activities of four cyclic opioid peptides with various sequence length/macrocycle size and N-methylamino acid residue content. N-Methylated amino acids were incorporated and cyclization was employed to enhance conformational rigidity to various extent. The effect of such modifications on ligand structure and binding properties were studied. The pentapeptide containing one endocyclic and one exocyclic N-methylated amino acid displayed the highest affinity to the mu-opioid receptor. This peptide was also shown to be a full agonist, while the other analogs failed to activate the mu opioid receptor. Results of molecular docking studies provided rationale for the explanation of binding properties on a structural basis.

Słowa kluczowe

opioid receptors, N-Methylated amino acids, Cyclic peptides, binding studies, Functional assays, Enzymatic stability, docking

Adres publiczny

http://dx.doi.org/10.1016/j.bmcl.2017.03.016

Strona internetowa wydawcy

http://www.elsevier.com

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