Tyr1-substituted and fluorescent Pya1-enkephalins bind strongly and selectively to mu and delta opiate receptors.
The fluorescent enkephalins in which an essential Tyr1 residue is replaced by L-1-pyrenylalanine (Pya) were synthesized and examined in the receptor binding assays. [Pya1, Leu5]Enkephalin and its methyl ester showed binding characteristics specific for the opiate receptors, exhibiting a potent inhibition of Tyr1-containing enkephalins. Surprisingly, the methyl ester displayed almost the same potencies to those of DAGO-enkephalin. This analog bound 24-fold more strongly to mu than to delta-receptors. C-terminal free analog Pya1-Enk-OH was delta-preferential with a fairly good affinity. These results indicate that Tyr1 in enkephalin is not necessary to recognition of the opiate receptors.
D000409:Alanine / Q000031:analogs & derivatives*; D000818:Animals; D001667:Binding, Competitive; D003461:Crystallography; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000378:metabolism*; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D011721:Pyrenes; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014443:Tyrosine
D004745:Enkephalins; D011721:Pyrenes; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D014443:Tyrosine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C047443:1-pyrenylalanine; D000409:Alanine