Antiovulatory Potency and Conformation of an Antagonist of the Luteinizing Hormone-Releasing Hormone Having Six D-Amino Acids
Open Access
- 1 July 1982
- journal article
- Published by Walter de Gruyter GmbH in Zeitschrift für Naturforschung B
- Vol. 37 (7) , 872-876
- https://doi.org/10.1515/znb-1982-0716
Abstract
[N-Ac-Thr 1 ,D-Phe 2,D-Trp 3,6]-LHRH was the model antagonist of LHRH, which was the basis for tho design, synthesis and bioassay of seven peptides having four, five and six D-amino acids, which resulted from three single, three double, and one triple introductions of D-amino acids in positions 4, 5 and 8 of the model. Only the analog with six D-amino acids, [N-Ac-Thr 1,D-Phe 2 ,D-Trp 3,D-Ser 4, D-Tyr 5 ,D-Trp 6 ,D-Arg 8]-LHRH, had antiovulatory activity which was higher than that of the model antagonist, i.e., 70% antiovulatory activity at 25 μg/rat compared with 50% activity at 50 μg/rat, respectively. Empirical energy calculations gave a conformational structure for [N-Ac-Thr 1,D-Phe 2,D-Trp 3, D-Ser 4,D-Tyr 5,D-Arg 6,D-Arg 8]-LHRH which is similar to that calculated for previous potent antagonists. These results are a basis of new designs of antagonists having D-sub-stituents in up to ten positions toward effective inhibitors of ovulation by the parenteral and oral routes of administration.Keywords
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