84809-70-1Relevant articles and documents
Deltorphin II analogues with 6-hydroxy-2-aminotetralin-2-carboxylic acid in position 1
Darula, Zsuzsanna,K?vér, Katalin E.,Monory, Krisztina,Borsodi, Anna,Makó, éva,Rónai, András,Tourwé, Dirk,Péter, Antal,Tóth, Géza
, p. 1359 - 1366 (2000)
Two approaches to the design of very active and highly selective δ opioid peptides were used to obtain new deltorphin analogues with altered hydrophobic and stereoelectronic properties. Deltorphin II analogues were synthesized with the substitution of Ile instead of Val at positions 5 and 6 in the address domain and 6-hydroxy-2-aminotetralin-2-carboxylic acid (Hat) instead of Tyr1 in the message domain. In the radioreceptor-binding studies, in which type-specific tritiated opioid ligands were used, (R)- and (S)-Hat- deltorphins exhibited similar K(i) values, revealing high δ selectivity. The peptides displayed agonist properties in the in vitro bioassay, with IC50 values in the subnanomolar range in the mouse vas deferens assay and in the micromolar or higher range in the guinea pig ileum assay, again demonstrating a high selectivity toward δ receptors. The agonist property of the new ligands was confirmed by means of [35S]GTPγS-binding experiments in membranes of the rat frontal cortex.
