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

Abstract

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

Rapid and Controllable Hydrogen/Deuterium Exchange on Aromatic Rings of α‐Amino Acids and Peptides

“…There are two major methods with which to prepare deuterated α‐amino acids and biologically active peptides with the label on the aromatic moiety. Halogen‐substituted aromatics have been converted into α‐amino acids through asymmetric synthesis, subjected to peptide synthesis, then halogen/deuterium exchange was achieved by hydrogenation (Scheme a) 2. However, this approach involves multistep syntheses.…”