A new potential affinity label for the opiate receptor.
D-Ala2-Leu5-enkephalin (DALA) was elongated with the methyl ester of melphalan (Mel), a nitrogen mustard on the C-terminus. The new derivative, DALA-Mel-OMe might be a potential affinity label of the opiate receptor. The compound shows high affinity in displacement experiments with an IC50 of 10 nM and 100 nM against 3H-D-Ala2-Leu5-enkephalin and 3H-naloxone, respectively. 10-100 microM of DALA-Mel-OMe causes a significant inhibition of 3H-naloxone binding, which effect can't be reversed by extensive washes. This irreversible blockade is significantly but only partially protected by high concentrations of naloxone and Leu-enkephalin. Our results suggest that DALA-Mel-OMe binds irreversibly to the opiate receptor, but nonspecific labelling also occurs.
D000345:Affinity Labels / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives*; D007700:Kinetics; D008558:Melphalan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D000345:Affinity Labels; D011957:Receptors, Opioid; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C040240:enkephalin-Leu, Ala(2)-melphalan methyl ester-; D008558:Melphalan