Binding characteristics of a series of dimeric tripeptide enkephalins for delta 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 alpha,omega-diaminoalkanes, NH2-(CH2)n-NH2 (n = 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22). The binding affinities of dimers for delta opiate receptors in rat brain were evaluated and compared with those for delta 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 delta receptors in rat brain and NG cells may have slight structural differences.
Shimohigashi
Y
Y
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.
Kodama
H
H
Costa
T
T
Lutz
R A
RA
Chen
H C
HC
Rodbard
D
D
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004745:Enkephalins / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*
D004745:Enkephalins; D011957:Receptors, Opioid