The properties of di- and tri-peptides containing 1,2,3,6tetrahydroisoquinoline-3-carboxyliacc id (Tic) in second position suggest that the message domain of opioid peptides can be composed of only two residues [Temussi, P. A., Salvadori, S., Amodeo, P., Guerrini, R., Tomatis, R., Lazarus, L. H., Picone, D. & Tancredi, T. (1994) Biochem. Biophys. Res. Commun. 198, 933-9391. As a crucial test of the possibility that the Tyr-Tic segment be a message domain in longer peptide sequences, we have inserted it in the sequences of two typical opioid peptides: [Leulenkephalin, a non-selective agonist, and dermorphin, a selective p agonist. Here we report the synthesis and biological activity of [~-Tic’]enkephalin, [~-Tic~]dermorphi[n~,- Tic’]dermorphin carboxylic acid and [~-Tic’]dermorphin: all [L-Tic’lpeptides were converted from agonists to &selective antagonists. The NMR conformational study in a dimethylsulfoxide/water cryoprotective mixture at low temperature shows diagnostic side-chain-side-chain NOES in the spectra of all [~-Tic’]peptides and hints that the 90” arrangement of the the two aromatic rings found in the cis-Tyr-L-Tic moiety, typical of N-methyl naltrindole and other 6-selective opiate antagonists, is responsible for the antagonist activity of all these peptides.

Conversion of Enkephalin and Dermorphin into δ‐Selective Opioid Antagonists by Single‐Residue Substitution

SALVADORI, Severo;GUERRINI, Remo;
1994

Abstract

The properties of di- and tri-peptides containing 1,2,3,6tetrahydroisoquinoline-3-carboxyliacc id (Tic) in second position suggest that the message domain of opioid peptides can be composed of only two residues [Temussi, P. A., Salvadori, S., Amodeo, P., Guerrini, R., Tomatis, R., Lazarus, L. H., Picone, D. & Tancredi, T. (1994) Biochem. Biophys. Res. Commun. 198, 933-9391. As a crucial test of the possibility that the Tyr-Tic segment be a message domain in longer peptide sequences, we have inserted it in the sequences of two typical opioid peptides: [Leulenkephalin, a non-selective agonist, and dermorphin, a selective p agonist. Here we report the synthesis and biological activity of [~-Tic’]enkephalin, [~-Tic~]dermorphi[n~,- Tic’]dermorphin carboxylic acid and [~-Tic’]dermorphin: all [L-Tic’lpeptides were converted from agonists to &selective antagonists. The NMR conformational study in a dimethylsulfoxide/water cryoprotective mixture at low temperature shows diagnostic side-chain-side-chain NOES in the spectra of all [~-Tic’]peptides and hints that the 90” arrangement of the the two aromatic rings found in the cis-Tyr-L-Tic moiety, typical of N-methyl naltrindole and other 6-selective opiate antagonists, is responsible for the antagonist activity of all these peptides.
1994
Tancredi, T; Salvadori, Severo; Amodeo, P; Picone, D; Lazarus, Lh; Bryant, Sd; Guerrini, Remo; Marzola, G; Temussi, Pa
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/470909
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