Tritiation of delta opioid-receptor selective antagonist dipeptide ligandswith extraordinary affinity containing 2 ', 6 ' dimethyltyrosine

Recently a new class of delta opioid antagonists has been discovered by usi ng Tyr-Tic sequence. The substitution of Tyr(1) by Dmt resulted in a new an alogue (H-Dmt-Tic-OH) with enhanced affinity and selectivity. Because of it s excellent property we chose if. for labelling with tritium. At the same t ime peptides containing Tic at position 2 undergo spontaneous diketopiperaz ine formation in some solvents, and they lose some of their binding ability . To avoid this unwanted side-reaction we synthetized the N-methylated anal ogue (N,N(Me)(2)-Dmt-Tic-OH), and it was more stable under storage conditio n, but delta affinity declined moderately. On the basis of this information we prepared diiodinated analogues of these dipeptides. Catalytic dehalotri tiation of precursors resulted in tritiated peptides. High specific radioac tivity, 44.67 Ci/mmol with [H-3]Dmt-Tic-OH and 59.88 Ci/mmol with N,N(Me)(2 )-[H-3]Dmt-Tic-OH were achieved.