Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Lutenizing hormone releasing factor ; related peptides
Patent
1989-06-26
1995-11-28
Warden, Jill
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Lutenizing hormone releasing factor ; related peptides
530328, 930130, C07K 723
Patent
active
054709474
ABSTRACT:
Antide is the decapeptide, N--Ac--D--2--Nal,D--pClPhe, D--3--Pal, Ser,NicLys, D--NicLys, Leu, ILys, Pro, D--Ala,NH.sub.2 which is an antagonist of luteinizing hormone releasing hormone (LHRH). This decapeptide, like others of the present invention, has high antiovulatory activity (AOA) and releases negligible histamine. Antide is scheduled for scale-up, safety testing and evaluation in the experimental primate and in clinical medicine. Numerous other peptides having structures related to Antide were prepared and tested. These peptides had variations primarily in positions 5, 6, 7, and 8. Of these, N--Ac--D--2--Nal, D--pClPhe,D--3--Pal,Ser,PicLys,cis--DpzACAla, Leu,ILys,pro,D--Ala--NH.sub.2 was one of the most potent and had higher antiovulatory activity than Antide, i.e. 73%/0.25 ug and 100%/0.5 ug vs. 36%/0.5 ug and 100%/1.0 ug. Antide showed significant, (p<0.001) duration of action, when injected at a dose of 10 ug, 44 hours before 50 ng of the agonist, [D--3--Qal.sup.6 ]--LHRH. Antide showed oral AOA at 600 ug (73%) and at 1200 ug (100%) with negligible difference being found between water and corn oil oral formulations.
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Bowers Cyril Y.
Feng Dong-Mei
Folkers Karl A.
Kubota Minoru
Ljungqvist Anders
Board of Regents , The University of Texas System
The Administrators of the Tulane Educational Fund
Warden Jill
Wessendorf T. D.
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