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Updated: May 18, 2026

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids
Published on: February 21, 2018
Opioid activity profiles of oversimplified peptides lacking in the protonable N-terminus
Rossella De Marco1, Alessandra Tolomelli, Santi Spampinato
1Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
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.
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