Szücs M, Di Gleria K, Medzihradszky K
Life Sci. 1983;33 Suppl 1:435-8. doi: 10.1016/0024-3205(83)90535-0.
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.
D-丙氨酸2-亮氨酸5-脑啡肽（DALA）与苯丙氨酸氮芥（Mel）的甲酯在C末端进行了延伸。新衍生物DALA-Mel-OMe可能是阿片受体的潜在亲和标记物。该化合物在置换实验中表现出高亲和力，对3H-D-丙氨酸2-亮氨酸5-脑啡肽和3H-纳洛酮的IC50分别为10 nM和100 nM。10-100 μM的DALA-Mel-OMe会导致3H-纳洛酮结合的显著抑制，这种效应不能通过大量洗涤来逆转。高浓度的纳洛酮和亮氨酸脑啡肽可显著但仅部分保护这种不可逆的阻断。我们的结果表明，DALA-Mel-OMe与阿片受体不可逆结合，但也会发生非特异性标记。
