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

Anna Adamska-Bartłomiejczyk, Anna Janecka, Márton Richárd Szabó, Maria Camilla Cerlesi, Girolamo Calo, Alicja Kluczyk, C. Tömböly, Attila Borics

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1644-1648
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number8
DOIs
Publication statusPublished - Apr 15 2017

Fingerprint

mu Opioid Receptor
Ligands
Amino Acids
Cyclic Peptides
Opioid Peptides
Cyclization
Rigidity
Peptides
Acids
In Vitro Techniques

Keywords

  • Binding studies
  • Cyclic peptides
  • Docking
  • Enzymatic stability
  • Functional assays
  • N-Methylated amino acids
  • Opioid receptors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Adamska-Bartłomiejczyk, A., Janecka, A., Szabó, M. R., Cerlesi, M. C., Calo, G., Kluczyk, A., ... Borics, A. (2017). Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues. Bioorganic and Medicinal Chemistry Letters, 27(8), 1644-1648. https://doi.org/10.1016/j.bmcl.2017.03.016

Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues. / Adamska-Bartłomiejczyk, Anna; Janecka, Anna; Szabó, Márton Richárd; Cerlesi, Maria Camilla; Calo, Girolamo; Kluczyk, Alicja; Tömböly, C.; Borics, Attila.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 8, 15.04.2017, p. 1644-1648.

Research output: Contribution to journalArticle

Adamska-Bartłomiejczyk, A, Janecka, A, Szabó, MR, Cerlesi, MC, Calo, G, Kluczyk, A, Tömböly, C & Borics, A 2017, 'Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues', Bioorganic and Medicinal Chemistry Letters, vol. 27, no. 8, pp. 1644-1648. https://doi.org/10.1016/j.bmcl.2017.03.016
Adamska-Bartłomiejczyk A, Janecka A, Szabó MR, Cerlesi MC, Calo G, Kluczyk A et al. Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues. Bioorganic and Medicinal Chemistry Letters. 2017 Apr 15;27(8):1644-1648. https://doi.org/10.1016/j.bmcl.2017.03.016
Adamska-Bartłomiejczyk, Anna ; Janecka, Anna ; Szabó, Márton Richárd ; Cerlesi, Maria Camilla ; Calo, Girolamo ; Kluczyk, Alicja ; Tömböly, C. ; Borics, Attila. / Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues. In: Bioorganic and Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 8. pp. 1644-1648.
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