Increased potency of antagonists of the luteinizing hormone releasing hormone which have D-3-Pal in position 6.
Ever increasing potency is an international goal for antagonists of the luteinizing hormone releasing hormone (LHRH). [N-Ac-D-2-Nal1,D-pClPhe2, D-3-Pal3,Ser4,Arg5,D-3-Pal6,Leu7,Arg8,Pro9,D- Ala10]-NH2 caused 60%/125 ng inhibition of ovulation in the rat, and appears to be the most potent antagonist yet described. Strategy of design was the replacement of D-Arg6 with D-3-Pal6 and of Tyr5 with Arg5. Replacing Arg5 with His5 reduced activity by 50% at 250 ng. Both the Arg5 and His5 analogs showed 100% inhibition of ovulation at 0.5 microgram. Of ten pairs of analogs with D-3-Pal6 and D-Arg6, 3/10 with D-3-Pal6 were more potent than those with D-Arg6. Histamine release was less for the D-3-Pal6 peptides of three pairs.
D000409:Alanine / Q000031:analogs & derivatives; D000596:Amino Acids; D000818:Animals; D001120:Arginine; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010060:Ovulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000596:Amino Acids; D007987:Gonadotropin-Releasing Hormone; C012787:3-pyridylalanine; D001120:Arginine; D000409:Alanine