Evidence of a peptide backbone contribution toward selective receptor recognition for leucine enkephalin thioamide analogs.
The in vitro opioid activities of a series of leucine enkephalin analogs containing a thioamide linkage in place of the peptide bond at various positions of the backbone were determined in mu- and delta-receptor-selective bio- and binding-assays. Thioamide substitution in the 1-2 position resulted in an inactive compound, whereas the same modification in the 2-3 and 4-5 position produced potency enhancement. Most interestingly, the 2-3 modified analog showed a 3 to 5 times higher preference for delta- over mu-receptors than natural leucine enkephalin. These results suggest that subtle backbone modifications can have a profound effect on receptor affinity and selectivity of biologically active peptides.
D000577:Amides / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000378:metabolism*
D000577:Amides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D013854:Thioamides; D004743:Enkephalin, Leucine