Opioid activity profiles of oversimplified peptides lacking in the protonable N-terminus.

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De Marco R, Tolomelli A, Spampinato S, Bedini A, Gentilucci L

Opioid activity profiles of oversimplified peptides lacking in the protonable N-terminus.

J Med Chem. 2012 Nov 26;55(22):10292-6. doi: 10.1021/jm301213s. Epub 2012 Oct 19.

PubMed ID

22995061 [ View in PubMed

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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 mu-opioid receptor affinity and selectivity. Conformational analysis suggested that 5 adopts in solution a beta-turn conformation.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Morphine	Mu-type opioid receptor	IC 50 (nM)	4.3	N/A	N/A	Details