Dansylated analogues of the opioid peptide [Dmt1]DALDA:: in vitro activity profiles and fluorescence parameters

Dansylated analogues of the potent and selective mu opioid peptide agonist [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe Lys-NH2; Dmt = 2',6'-dimethyltyrosine) were prepared either by substitution of N-beta-dansyl-alpha,beta-diaminopropionic acid or N-epsilon-dansyl-lysine for Lys(4), or by attachment of a dansyl group to the C-terminal carboxamide function via a linker. All three analogues displayed high mu agonist potency in vitro and the C-terminally dansylated one retained significant mu receptor selectivity. The three analogues showed interesting differences in their fluorescence emission maxima and quantum yields, indicating that the dansyl group in two of them was engaged in intramolecular hydrophobic interactions. These dansylated [Dmt(1)]DALDA analogues represent valuable tools for binding studies, cellular uptake and intracellular distribution studies, and tissue distribution studies.