Comparative binding properties of linear and cyclic δ-selective enkephalin analogues: [3H]-[D-Thr2, Leu5] enkephalyl-Thr6 and [3H]-[D-Pen2, D-Pen5] enkephalin

AbstractThe range of δ-selectivity of linear and cyclic analogues of enkephalin in rat brain was found to be: [D-Pen2,L-Pen5] enkephalin (DPLPE) > [D-Pen2,D-Pen5] enkephalin (DPDPE) > [D-Thr2, Leu5] enkephalyl-Thr6 (DTLET) > [D-Ser2, Leu5] enkephalyl-Thr6 (DSLET). Saturation experiments performed with [3H]DPDPE and [3H]DTLET in NG108-15 cells and rat brain showed similar binding capacities for both the ligands, but the δ-affinity of [3H]DTLET (KD ≈ 1.2 nM) was much better than that of [3H]DPDPE (KD ≈ 7.2 nM). The rather low δ-affinity of DPDPE induced high experimental errors cancelling the benefit of its better δ-selectivity. Binding experiments in rat or guinea-pig brains showed, in both cases, the better δ-selectivity of [3h]dtlet compared to [3h]slet. The former peptide remains at this time the most appropriate radioactive probe for binding studies of δ-receptor