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, GlyNH2). Ac-D-Trp-PheNH2 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. © 2012 American Chemical Society.
Opioid activity profiles of oversimplified peptides lacking in the protonable N-terminus
De Marco R.;
2012-01-01
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, GlyNH2). Ac-D-Trp-PheNH2 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. © 2012 American Chemical Society.File in questo prodotto:
File | Dimensione | Formato | |
---|---|---|---|
J Med Chem 2012.pdf
accesso aperto
Descrizione: Articolo principale
Tipologia:
Versione Editoriale (PDF)
Licenza:
Creative commons
Dimensione
230.33 kB
Formato
Adobe PDF
|
230.33 kB | Adobe PDF | Visualizza/Apri |
j med chem, 2012, supporting information.pdf
accesso aperto
Tipologia:
Versione Editoriale (PDF)
Licenza:
Creative commons
Dimensione
62.37 kB
Formato
Adobe PDF
|
62.37 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.