Selectivity of minimum structure enkephalins.
The biological activity of 45 deletion tetrapeptide-, tripeptide- and dipeptide enkephalin analogs has been determined in the stimulated mouse vas deferens (MVD) and guinea pig ileum (GPI) assays. A comparison of the GPI and MVD activities of these 45 minimum structure analogs indicates a high degree of mu receptor specificity. The greatest selectivity is found in the dipeptide amide Tyr-DAla-benzylamide, while high selectivity was also found in the tetrapeptides Tyr-DAla-Trp-Leu-NH2 and Tyr-Aib-Phe-Leu-NH2, and in two tripeptides Tyr-DTrp-Phe-NH2 and Tyr-Pro-Phe-NH2. The dipeptide amide Tyr-DAla-(3-phenyl-1-propyl)-amide (DAPPA), which has been shown to possess high in vitro potency (on the stimulated GPI) and in vivo potency (analgesia in mice after icv administration), is shown to have 60 times the activity in the GPI assay relative to its activity on the stimulated MVD, further indicating the correlation between mu-receptor activity and analgesia.
D000818:Animals; D001681:Biological Assay; D004745:Enkephalins / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects*
D004745:Enkephalins; D009842:Oligopeptides