Superiority of an antagonist of the luteinizing hormone releasing hormone with emphasis on arginine in position 8, named Argtide.
In the research for more potent antagonists of the luteinizing hormone releasing hormone (LHRH), 13 new peptides with emphasis on arginine in position 8 were designed, synthesized and tested for anti-ovulatory activity (AOA). Two very potent analogs were achieved. N-Ac-D-3-Qal, D-pClPhe, D-3-Pal, Ser, cis-PzACA1a, D-PicLys, Leu, Arg, Pro, D-AlaNH2 showed 63% AOA at 0.125 microgram and 89% at 0.25 microgram, and an ED50 of 30.8 +/- 0.59 and presently may be the most promising antagonist reported. It is named Argtide. N-Ac-D-3-Qal, D-pClPhe, D-3-Pal, Ser, cis-PzACA1a, D-PicLys, Val, Arg, Pro, D-AlaNH2 showed 18% AOA at 0.125 microgram. Arg8 in antagonists may be significant for receptor binding.
Janecka
A
A
Institute for Biomedical Research, University of Texas, Austin 78712.
Ljungqvist
A
A
Bowers
C
C
Folkers
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D006224:Cricetinae; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides; D051381:Rats; D011966:Receptors, LHRH / Q000378:metabolism
D009842:Oligopeptides; D011966:Receptors, LHRH; C071339:argtide; C071340:N-acetyl-3-(3-quinolyl)alanyl-3-(4-chlorophenyl)alanyl-3-(3-pyridyl)alanyl-seryl-3-(4-pyrazinylcarbonylaminocyclohexyl)alanyl-N(epsilon)picolinoyllysyl-valyl-arginyl-prolyl-alaninamide; D007987:Gonadotropin-Releasing Hormone; D001120:Arginine