Peptide hormones. 137. Structural requirements in positions 1, 2, 3, and 6 of the luteinizing hormone-releasing hormone (LH-RH) for antiovulatory activity
- 1 July 1979
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 22 (7) , 774-777
- https://doi.org/10.1021/jm00193a005
Abstract
Analogs (16) of the luteinizing hormone-releasing hormone (LH-RH) were synthesized by the solid-phase method. Apparently the substitution of D-Trp [tryptophan] into position 3 of [D- < Glu1 [D-pyroglutamic acid], D-Phe2, amino acid3,D-Phe6]-LH-RH significantly enhanced the antiovulatory potency [rats] but substitution by Pro [proline], N-Me-Phe [N-methyl phenylalanine], N-Me-Leu [N-methyl-leucine], or L-Trp reduced antiovulatory activity. The substitution of L < Glu in L- < Glu in position 1 of [D-Phe2,Pro3,D-Phe6]-LH-RH by cyclohexylcarbonyl (Chc), benzoyl (Bz), Ac [acetyl], Hyp [hydroxyproline], Ac-Met [acetyl-methionine], hydrogen, Pro and D- < Glu residues and the substitution of D-Phe in position 2 by D-Trp, D-His, D-Phg [phenylgycyl] and L-Phe residues caused analog with no antiovulatory activity at 750 .mu.g/rat. Structural requirements for the design of inhibitors of higher potency were discussed.This publication has 8 references indexed in Scilit:
- A new category of ovulation inhibitors linear LH-RH analogues having more than ten residuesBiochemical and Biophysical Research Communications, 1979
- An antiovulatory decapeptide of higher potency which has an -amino acid (Ac-Pro) in position 1Biochemical and Biophysical Research Communications, 1978
- Peptide hormones. 109. Inhibitory analogs of the luteinizing hormone-releasing hormone having D-aromatic residues in positions 2 and 6 and variation in position 3Journal of Medicinal Chemistry, 1978
- Nonapeptide ethylamide inhibitors of the luteinizing hormone-releasing hormone (LH-RH) having a D-alanyl residue in position 6 and variations at positions 2 and 3Journal of Medicinal Chemistry, 1977
- On the importance of position one of ovulation inhibitors, as based on studies on [D-Phe2, Pro3, D-Phe6]-LHRHBiochemical and Biophysical Research Communications, 1977
- Presence of proline in positions 3 for potent inhibition of the activity of the luteinizing hormone releasing hormone and of ovulationBiochemical and Biophysical Research Communications, 1976
- Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. 2. Tetrapeptide and decapeptide analoguesJournal of the American Chemical Society, 1976
- Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. 1. Native decapeptideJournal of the American Chemical Society, 1976