125I-DPDYN, monoiodo[D-Pro 10]dynorphin(1–11): A highly radioactive and selective probe for the study of kappa opioid receptors

Abstract

The mono- and diiodinated derivatives of the κ-selective ligand [D-Pro 10]dynorphin(1–11), DPDYN, were prepared. Their binding properties at the three opioid receptor types (μ, δ and κ) were examined and compared to those of the parent peptide. The monoiodo derivative shows a general although moderate decrease in affinity and retains high κ selectivity ( K Iμ K Iκ = 48 and K Iδ K Iκ = 140 ). The binding properties of the diiodo derivative are found to be dramatically decreased. Radioiodination of DPDYN leads to the monoiodinated peptide with high specific activity (700–800 Ci/mmol). In guinea-pig cerebellum membranes, a κ-specific tissue, [ 125I]-labelled monoiodo[D-Pro 10]dynorphin(1–11), 125I-DPDYN, interacts specifically and reversibly with a single class of binding sites (B max = 118 fmol/mg protein) with a high affinity (K D = 0.12 nM from equilibrium experiments, 0.18 nM from kinetics studies). Therefore, because of its high specific radioactivity, high affinity and reasonably good selectivity, 125I-DPDYN designates itself as the probe of the k-opioid receptor type.