[3H]DSTBULET, a new linear hexapeptide with both an improved selectivity and a high affinity for delta-opioid receptors.

The binding properties of the new agonist Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr, DSTBULET, in rat brain tissue shows that insertion of a bulky t.butyl group into the sequence of DSLET leads to a conformationally-induced large increase in selectivity for delta opioid receptors (KI(delta)/KI(mu) = 0.012). In addition to its similar selectivity to that of the cyclic enkephalins DPDPE and DPLPE, the affinity of [3H]DSTBULET for delta sites (KD = 2.9 nM) is significantly better than that of [3H]DPDPE (KD approximately 10.5 nM) or DPLPE (KI (delta) approximately 19 nM). DSTBULET is therefore the most appropriate probe for both binding studies and pharmacological investigations of delta-receptors as illustrated by a comparison of the analgesic properties of DAGO, DSTBULET and DPLPE.