Shimohigashi Y, Waki M, Izumiya N, Costa T, Herz A, Kurono M, Yagi K
Biochem Int. 1986 Aug;13(2):199-203.
DAGO-enkephalin ([ D-Ala2, MePhe4, Gly-ol5]enkephalin), a highly selective ligand for mu opiate receptors, was dimerized with a series of alpha,omega-alkanedioic acids (n = 2-12) at the OH-terminus. In the radioligand receptor binding assays with rat brain, most of the DAGO-enkephalin dimers with cross-linking methylene chain n (DEDn) were more potent than DAGO monomer. For delta receptors, affinity of DEDn was maximized with n = 8, which might be related to an optimal distance between two binding sites. For mu receptors, an increase in chain length resulted in a progressive loss of potency. Although all of DEDn are considerably mu-selective, with a mu/delta ratio of 15-50, DEDn exhibited fairly flat binding curves with 15-50% smaller sloped than that of DAGO, suggesting that the dimers interact more strongly with one of the possible two mu binding sites.
DAGO-脑啡肽（[D-丙氨酸2，甲基苯丙氨酸4，甘醇5]脑啡肽）是一种对μ阿片受体具有高度选择性的配体，它在OH末端与一系列α，ω-链烷二酸（n = 2-12）二聚化。在大鼠脑的放射性配体受体结合试验中，大多数带有交联亚甲基链n的DAGO-脑啡肽二聚体（DEDn）比DAGO单体更有效。对于δ受体，DEDn的亲和力在n = 8时达到最大值，这可能与两个结合位点之间的最佳距离有关。对于μ受体，链长的增加导致效力逐渐丧失。尽管所有的DEDn都具有相当高的μ选择性，μ/δ比值为15-50，但DEDn的结合曲线相当平缓，斜率比DAGO小15-50%，这表明二聚体与两个可能的μ结合位点之一的相互作用更强。
