SYNTHESIS AND BINDING CHARACTERISTICS OF THE HIGHLY SELECTIVE RADIOLABELED DELTORPHIN ANALOGS CONTAINING 2-AMINOTETRALIN-2-CARBOXYLIC ACID IN POSITION-3

Following the description of [H-3]Ile(5,6)deltorphin II, when it was r eported that changes in hydrophobicity at positions 5 and 6 give rise to analogues with increased delta-receptor affinity and selectivity, n ew conformationally restricted deltorphin analogues were designed. A s ynthetic amino acid, 2-aminotetralin-2-carboxylic acid (Atc), was intr oduced at position 3 instead of Phe in Ile(5,6)deltorphin I and II, an d the resultant compounds were prepared in tritiated form, Opioid bind ing sites specific for [H-3]s-Atc(3),Ile(5,6)deltorphin I and [H-3]R-A tc3,Ile(5,6)deltorphin II were characterized in rat brain membranes, T heir binding was saturable, stereoselective and inhibited by delta-sel ective ligands with high potency. They labelled single class of opioid sites at 35 degrees C with high affinity (K-d approximate to 0.3 nM), B-max values of 130 fmol/mg protein, and very low non-specific bindin g was observed, Both tritiated deltorphin analogues showed delta-recep tor specificity in rat brain, therefore they could represent excellent new radioligands for investigating the complexity of the opioid recep tor systems.