Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues

Giordano Lesma, Severo Salvadori, Francesco Airaghi, Engin Bojnik, A. Borsodi, Teresa Recca, Alessandro Sacchetti, Gianfranco Balboni, Alessandra Silvani

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

This study reports on new pharmacologically active endomorphin-2 analogues, incorporating β 2-hPhe, β 3-hPhe and β 3-hTic unnatural amino acids in the place of the Phe 3-Phe4residues. Such α, β-hybrid analogues were designed to exploit the great potential of β-amino acids in generating conformational variation at the key positions 3 and 4, with the aim of evaluating the effect on the opioid binding affinity. Ligand-stimulated binding assays indicated that some analogues retained a significant affinity, especially for the δ receptor. 1H NMR and molecular modelling suggested the predominance of bent structures for all compounds. The molecular docking with the μ-opioid receptor model was also performed, highlighting a common binding mode for active compounds and helping to rationalize the observed structure-activity data.

Original languageEnglish
Pages (from-to)19-31
Number of pages13
JournalMolecular Diversity
Volume17
Issue number1
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Amino acids
Pharmacology
analogs
Amino Acids
Molecular modeling
amino acids
affinity
evaluation
Opioid Receptors
synthesis
Opioid Analgesics
Assays
Ligands
Nuclear magnetic resonance
nuclear magnetic resonance
ligands
endomorphin 2
Proton Magnetic Resonance Spectroscopy

Keywords

  • Beta-amino acid
  • Endomorphin-2
  • Molecular docking
  • Molecular modelling
  • Opioid receptor
  • Peptidomimetic

ASJC Scopus subject areas

  • Molecular Biology
  • Drug Discovery
  • Information Systems
  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Catalysis
  • Organic Chemistry

Cite this

Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues. / Lesma, Giordano; Salvadori, Severo; Airaghi, Francesco; Bojnik, Engin; Borsodi, A.; Recca, Teresa; Sacchetti, Alessandro; Balboni, Gianfranco; Silvani, Alessandra.

In: Molecular Diversity, Vol. 17, No. 1, 02.2013, p. 19-31.

Research output: Contribution to journalArticle

Lesma, G, Salvadori, S, Airaghi, F, Bojnik, E, Borsodi, A, Recca, T, Sacchetti, A, Balboni, G & Silvani, A 2013, 'Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues', Molecular Diversity, vol. 17, no. 1, pp. 19-31. https://doi.org/10.1007/s11030-012-9399-5
Lesma, Giordano ; Salvadori, Severo ; Airaghi, Francesco ; Bojnik, Engin ; Borsodi, A. ; Recca, Teresa ; Sacchetti, Alessandro ; Balboni, Gianfranco ; Silvani, Alessandra. / Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues. In: Molecular Diversity. 2013 ; Vol. 17, No. 1. pp. 19-31.
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