[ 3 H]UR-JG102-A Radiolabeled Cyclic Peptide with High Affinity and Excellent Selectivity for the Neuropeptide Y Y 4 Receptor.

The family of human neuropeptide Y receptors (YRs) comprises four subtypes (YR, YR, YR, and YR) that are involved in the regulation of numerous physiological processes. Until now, YR binding studies have been predominantly performed in hypotonic sodium-free buffers using I-labeled derivatives of the endogenous YR agonists pancreatic polypeptide or peptide YY. A few tritium-labeled YR ligands have been reported; however, when used in buffers containing sodium at a physiological concentration, their YR affinities are insufficient. Based on the cyclic hexapeptide UR-AK86C, we developed a new tritium-labeled YR radioligand ([H]UR-JG102, [H]). In sodium-free buffer, [H] exhibits a very low YR dissociation constant ( 0.012 nM). In sodium-containing buffer (137 mM Na), the YR affinity is lower ( 0.11 nM) but still considerably higher compared to previously reported tritiated YR ligands. Therefore, [H] represents a useful tool compound for the determination of YR binding affinities under physiological-like conditions.