title: Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues.
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)-Phe(4)residues. 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. (1)H 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.
authors.affiliation: Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, via G, Venezian 21, 20133 Milan, Italy.
authors.forename: Giordano
authors.initials: G
authors.lastname: Lesma
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Francesco
authors.initials: F
authors.lastname: Airaghi
authors.forename: Engin
authors.initials: E
authors.lastname: Bojnik
authors.forename: Anna
authors.initials: A
authors.lastname: Borsodi
authors.forename: Teresa
authors.initials: T
authors.lastname: Recca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sacchetti
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Silvani
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D009842:Oligopeptides; D011957:Receptors, Opioid; C105294:endomorphin 2