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PubMed · 8117299

Selective opioid dipeptides.

P A Temussi·S Salvadori·P Amodeo·C Bianchi·R Guerrini·R Tomatis·L H Lazarus·D Picone·T Tancredi
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Abstract

The surprising change of selectivity induced by the change of chirality in peptides containing the tetrahydro-3-isoquinoline carboxylic acid (Tic) in second position, interpreted as a conformational preference induced on the Tyr-Xaa-Phe domain, can instead be attributed to the Tyr-Tic message domain. The relative spatial disposition of the aromatic ring of delta-selective non peptidic opiates is compatible with a message domain, in opioid peptides, of only two residues. This hypothesis was tested through the synthesis of Tyr-L-Tic-NH2, Tyr-D-Tic-NH2, Tyr-L-Tic-Ala-NH2, Tyr-L-Tic-Ala-OH and Tyr-D-Tic-Ala-NH2. Peptides containing Tyr-L-Tic- behave as very selective delta antagonists and those containing Tyr-DTic- as non selective agonists. This is the first case of opioid peptides containing a two-residue message domain and of opioid dipeptides with substantial opioid activity.

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Amino Acid SequenceAnimalsBinding, CompetitiveBrainCell MembraneDipeptidesEnkephalin, Ala(2)-MePhe(4)-Gly(5)-Enkephalin, D-Penicillamine (2,5)-EnkephalinsGuinea PigsIleumIn Vitro TechniquesIsoquinolinesKineticsModels, MolecularMolecular Sequence DataMuscle ContractionMuscle, SmoothNarcoticsOligopeptidesProtein ConformationRadioligand AssayRatsReceptors, Opioid, deltaReceptors, Opioid, muStereoisomerismStructure-Activity RelationshipSynaptosomesTetrahydroisoquinolinesJournal Article

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BibTeXRIS

P A Temussi, S Salvadori, P Amodeo, C Bianchi, R Guerrini, R Tomatis, L H Lazarus, D Picone, T Tancredi. 1994-02-15. Selective opioid dipeptides.. https://doi.org/10.1006/bbrc.1994.1133

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