Synthesis of a potent enkephalin analog, Tyr-D-Thr-Gly-Phe-delta 3 Pro-NH2, and some of its biological activities.
The enkephalin analog, H-Tyr-D-Thr-Gly-Phe-delta 3 Pro-NH2 X HCl (VI) ([D-Thr2, delta 3 Pro5]-enkephalinamide), has been synthesized by conventional methods in solution and purified to homogeneity by reversed phase HPLC. The analog is a potent analgesic agent. For evaluation of some of its biological activity a related compound [D-Thr2, Thz5]-enkephalinamide (XI) was also synthesized in solution. Anti-diarrhea activity was evaluated in mice by the intravenous route for anti-DL-5-hydroxytryptophan (5-HTP) induced diarrhea activity. Analgesic activity was assayed by the method of Nilsen in mice using the intravenous route, and by a modified tail flick test in rats and the acetic acid writhing test in mice following subcutaneous administration. Within the constraints of the assays the two analogs are approximately equipotent. Both are less active than [D-Ala2, MePhe4, Met(0)ol]-enkephalinol (XII). Earlier receptor binding studies of compound XI indicated enhanced affinity for the mu receptor and little for the delta receptor. By comparison this may also be the case for compound VI.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003967:Diarrhea / Q000188:drug therapy*; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009904:Optical Rotation; D013329:Structure-Activity Relationship; D053778:Thiazolidines
D000700:Analgesics; D004745:Enkephalins; D007202:Indicators and Reagents; D053778:Thiazolidines; C033339:enkephalin, Thr(2)-Thz(5)-GlyNH2(3)-; D009020:Morphine; C051118:enkephalinamide, Thr(2)-delta(3)Pro(5)-