Interaction of dimers of inactive enkephalin fragments with mu opiate receptors.
Dimeric analogues of the inactive enkephalin fragment Tyr-D-Ala-Gly were synthesized by cross-linking with alkanediamine at the C-terminus. Biological evaluation of these dimers (H-Tyr-D-Ala-Gly-NH)2.(-CH2-)n (DTREn), where n = 0-6, revealed that the fragment inactive for mu receptors was activated by its dimerization, with the maximum activation found with DTRE2, and that the dimer was highly mu-selective. So-called "handicapped" dimers, which lack one of the essential groupings required for enkephalin activity, were found to be far less active, indicating that the dimer interacts bivalently with mu receptors. It seems, therefore, that mu opiate receptors contain at least two equivalent binding sites which are extremely close to each other.
D000818:Animals; D004745:Enkephalins / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D013329:Structure-Activity Relationship
D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu