A novel side-chain-linked antiparallel cyclic dimer of enkephalin.
The dimeric cyclic enkephalin analog, (H-Tyr-D-Lys-Gly-Phe-Glu-NH2)2, was isolated as a second major component from the crude product obtained in a solid-phase synthesis of the corresponding cyclic monomer, H-Tyr-D-Lys-Gly-Phe-Glu-NH2. In comparison with [Leu5]enkephalin the cyclic dimer is about equipotent in assays representative for mu-opioid receptor interactions and 1/10 as potent at the delta-receptor. The fact that the enkephalin dimer shows a receptor selectivity pattern distinct from that of the cyclic monomer and of the corresponding linear analog suggests that cyclodimerization via side-chain linkages might be generally useful as a means to produce shifts in the activity profiles of peptide hormones and neurotransmitters.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D046911:Macromolecular Substances; D010456:Peptides, Cyclic / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004745:Enkephalins; D046911:Macromolecular Substances; D010456:Peptides, Cyclic; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; C046950:(H-Tyr-Lys-Gly-Phe-Glu-NH2)2