Abstract
Many synthetic antagonists of LHRH having pituitary receptor binding affinities of 10 to 20 times that of LHRH itself have been made. Generally, the best antagonists have an ED50 of about one microgram per animal in the rat antiovulatory assay. Most of these highly effective antagonists have a D-arginine residue in position 6 which, with the L-arginine8 of the native molecule and with a hydrophobic cluster of residues in the N-terminal part of the molecule, appears to be a potent canbination for the release of histamine from mast cells.
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Schmidt, F., Sundaram, K., Thau, R.B. and Bardin, C. W. [Ac-D-Nal (2)1, 4F-D-Phe2, D-Trp3, D-Arg6]-LHRH, a potent antagonist of LHRH, produces transient edema and behavioral changes in rats. Contraception, 29, 283 (1984).
Theoharides, T.C. and Douglas, W.W. Mast cell histamine secretion in response to somatostatin analogues: structural considerations. Eur. J. Pharmacol., 73, 131 (1981).
Roeske, R.W., Chaturvedi, N., Rivier, J., Vale, W., Porter, J. and Perrin, M. Substitution of Arg5 for Tyr5 in GhRH antagonists. In: “Peptides: Structure and Function.” C.M. Deber, V.J. Hruby and K.D. Kopple (Eds.), Pierce Chemical Co., Rockford, IL, 1985, p. 561.
Momany, F.A. Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. 1. Native decapeptide. J. Am. Chem. Soc., 98, 2990 (1976).
Freidinger, R.M., Veber, D.F., Perlow, D.S., Brooks, J.R. and Saperstein, R. Bioactive conformation of luteinizing hormone-releasing hormone: Evidence from a conformationally constrained analog. Science, 210, 656 (1980).
Nestor, J.J., Jr., Ho, T.L., Tahilramani, R., McRae, G.E. and Vickery, B.H. Long-acting LHRH agonists and antagonists. In: “LHRH and Its Analogues,” F. Labrie, A. Belanger, A. Dupont (Eds). Elsevier, Amsterdam, 1984, p. 24.
Nestor, J.J., Jr., Ho, T.L., Tahilramani, R., Horner, B.L., Simpson, R. A., Jones, G.H., McRae, G.I. and Vickery, B.H. LHRH agonists and antagonists containing very hydrophobic amino acids. In: “LHRH and Its Analogs: Contraceptive and Therapeutic Applications,” B.H. Vickery, J.J. Nestor, Jr. and E.S.E. Hafez (Eds.), MTP Press, Boston, 1984, p. 23.
Rivier, J.E., Porter, J., Rivier, C.L., Perrin, M., Corrigan, A., Hook, W.A., Siraganian, R.P. and Vale, W.W. New effective gonadotropin releasing hormone antagonists with minimal potency for histamine release in vitro. J. Med. Chem., 29, 1846 (1986).
Folkers, K., Bowers, C., Shaobo, X., Tang, P. and Kubota, M. Increased potency of antagonists of the luteinizing hormone releasing hormone which have D-3-Pal in position 6. Biochem. Biophys. Res. Comm., 137, 709 (1986).
Prasad, K.U., Roeske, R. W., Weitl, F. L., Vilchez-Martinez, J.H. and Schally, A.V. Structure-activity relationships in luteinizing hormone-releasing hormone. J. Med. Chem., 19, 492 (1976).
Jasani, B., Kreil, G., Mackler, B.F. and Stanworth, D.R. Further studies on the structural requirements for polypeptide-mediated histamine release from rat mast cells. Biochem. J. 181, 623 (1979).
Stanworth, D.R., Kings, M., Roy, P., Moran, J. and Moran, D. Synthetic peptides comprising sequences of the human immunoglobulin E heavy chain capable of releasing histamine. Biochem. J., 180, 665 (1979).
Corbin, A. and Beattie, C.W. Inhibition of the pre-ovulatory proestrous gonadotropin surge, ovulation and pregnancy with a peptide analogue of luteinizing hormone releasing hormone. Endocr. Res. Commun., 2, 1 (1975).
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Roeske, R.W., Chaturvedi, N.C., Hrinyo-Pavlina, T., Kowalczuk, M. (1987). LHRH Antagonists with Low Histamine Releasing Activity. In: Vickery, B.H., Nestor, J.J. (eds) LHRH and Its Analogs. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-3229-6_2
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DOI: https://doi.org/10.1007/978-94-009-3229-6_2
Publisher Name: Springer, Dordrecht
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