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-GlyNH2 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.

R. De Marco, A. Tolomelli, S. Spampinato, A. Bedini, L. Gentilucci (2012). Opioid Activity Profiles of Oversimplified Peptides Lacking in the Protonable N-Terminus. JOURNAL OF MEDICINAL CHEMISTRY, 55(22), 10292-10296 [10.1021/jm301213s].

Opioid Activity Profiles of Oversimplified Peptides Lacking in the Protonable N-Terminus

DE MARCO, ROSSELLA;TOLOMELLI, ALESSANDRA;SPAMPINATO, SANTI MARIO;BEDINI, ANDREA;GENTILUCCI, LUCA
2012

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-GlyNH2 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
R. De Marco, A. Tolomelli, S. Spampinato, A. Bedini, L. Gentilucci (2012). Opioid Activity Profiles of Oversimplified Peptides Lacking in the Protonable N-Terminus. JOURNAL OF MEDICINAL CHEMISTRY, 55(22), 10292-10296 [10.1021/jm301213s].
R. De Marco; A. Tolomelli; S. Spampinato; A. Bedini; L. Gentilucci
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/129888
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