title: Opioid activity profiles of oversimplified peptides lacking in the protonable N-terminus.
abstract: Recently, we described cyclopeptide opioid agonists containing the d-Trp-Phe sequence. To expand the scope of this atypical pharmacophore, we tested the activity profiles of the linear peptides Ac-Xaa-Phe-Yaa (Xaa = l/d-Trp, d-His/Lys/Arg; Yaa = H, GlyNH(2)). Ac-d-Trp-PheNH(2) appeared to be the minimal binding sequence, while Ac-d-Trp-Phe-GlyNH(2) emerged as the first noncationizable short peptide (partial) agonist with high μ-opioid receptor affinity and selectivity. Conformational analysis suggested that 5 adopts in solution a β-turn conformation.
authors.affiliation: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: De Marco
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tolomelli
authors.forename: Santi
authors.initials: S
authors.lastname: Spampinato
authors.forename: Andrea
authors.initials: A
authors.lastname: Bedini
authors.forename: Luca
authors.initials: L
authors.lastname: Gentilucci
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D003500:Cyclization; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000701:Analgesics, Opioid; D010446:Peptide Fragments; D017450:Receptors, Opioid, mu; D000242:Cyclic AMP