Orthogonal solid-phase synthesis of a monobiotinylated analog of neuropeptide Y

Analogs of Neuropeptide Y (NPY) were synthesized with conventional Boc/benzyl protective group strategy. Instead of Asn7 in the native sequence, Boc-Lys(Alloc)-OH was incorporated. At the end of the synthesis the Alloc group was selectively removed by palladium-catalyzed hydrostannolysis and biotin coupled to the epsilon-amino group of Lys7. After cleavage and characterization with plasma desorption mass spectrometry the N epsilon,7-biotinyl-[Lys7]-NPY and the nonbiotinylated analog [Lys7]-NPY were investigated as ligands to the NPY receptor from rat cerebral cortex. Both analogs were found to be high affinity ligands to the NPY receptor and bound with essentially the same affinity as unmodified NPY.