Endocrinology, Vol 110, 1445-1447, Copyright © 1982 by Endocrine Society

ARTICLES

Peptide antagonists of LH-RH: large increases in antiovulatory activities produced by basic D-amino acids in the six position

DH Coy, A Horvath, MV Nekola, EJ Coy, J Erchegyi and AV Schally

It has been assumed, usually with good reason, that D-amino acids with large aromatic side-chains must be present in position 6 of both LH-RH superagonists and antagonists for the highest levels of biological activity to be reached. However, using one of a recent generation of potent lH-RH inhibitory analogs as a model, we have found that the insertion of D-lysine or, better still, D-arginine in this position results in greater antiovulatory activity in the rat over corresponding D-phenylalanine6- and D-tryptophan6-analogs. For instance, [Ac-D-p-Cl- Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LH-RH exhibits antiovulatory activity at a dose of 750 ng per animal and appears to be the first competitive antagonist with activity in the nanogram region in vivo. This effect seems to be highly dependent on the degree of basicity of the amino acid side-chain since D-amino acids with neutral or acidic groups produced far less active compounds.

This article has been cited by other articles:

				A. Leanos-Miranda, A. Ulloa-Aguirre, L. A Cervini, J. A. Janovick, J. Rivier, and P M. Conn Identification of new gonadotrophin-releasing hormone partial agonists. J. Endocrinol., June 1, 2006; 189(3): 509 - 517. [Abstract] [Full Text] [PDF]

				M. Nekola, A Horvath, L. Ge, D. Coy, and A. Schally Suppression of ovulation in the rat by an orally active antagonist of luteinizing hormone-releasing hormone Science, October 8, 1982; 218(4568): 160 - 162. [Abstract] [PDF]