Synthesis of [2,6-3H2-Tyr1]leucine-enkephalin

Abstract

The synthesis of [2,6-³H₂-Tyr¹]leucine-enkephalin by the catalytic tritiation of [2,6-dibromo-Tyr¹]leucine-enkephalin is described. The precursor amino acid, 2,6-dibromo-DL-tyrosine, was synthesized in three steps from 2,6-dibromo-4-methoxytoluene. The protected [2,6-dibromo-Tyr¹]leucine-enkephalin derivative was prepared by solid-phase synthesis, followed by epimeric resolution on HPLC. The peptide was tritiated catalytically to yield [³H-Tyr¹]leucine-enkephalin with a specific radioactivity of 1.37 TBq/mmol. The distribution of tritium was investigated by HPLC with radioisotope detection following enzymatic hydrolysis, and confirmed that the tritium label was entirely located at the tyrosine residue.