Binding characteristics of a series of dimeric tripeptide enkephalins for δ opiate receptors in rat brain and NG108–15 cells

The N‐terminal tripeptide enkephalin analogue, Tyr‐ D ‐Ala‐Gly, was dimerized at the C‐terminus systematically with a series of α,ω‐diaminoalkanes, NH 2 (CH 2 ) n NH 2 ( n = 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22). The binding affinities of dimers for δ opiate receptors in rat brain were evaluated and compared with those for δ receptors in NG108–15 cells. Although the monomeric tripeptide amide was almost inactive, dimers showed a dramatic increase in binding affinity (8–900 times). The enhancement of affinity was apparently related to the number of methylene chains in the crosslinking spacer moiety, and it was maximal at n = 14–18 in the rat brain. In NG cells the activity increased progressively from n = 2 to n = 22 without reaching any apparent peak. These results suggest that δ receptors in rat brain and NG cells may have slight structural differences.