Abstract
A series of reduced-size analogs of LHRH was designed with the length varying from nine to two amino acids. These compounds were tested in vitro for the LH suppression in cultured rat pituitary cells treated with 1 ng of LHRH. The best analogs were also tested in vivo for their antiovulatory activity in rats. It appeared that terminal amino acids as well as the presence of Arg or ILys in the sequence are both crucial for the antagonism. The most potent antagonist in this series was a heptapeptide, AcDNal-Ser-Tyr-DNal-Leu-Arg-ProNHEt, which completely inhibited LH release at the dose 0.1 microgram and inhibited ovulation at 1000 micrograms/rat. For fragments shorter than heptapeptide the inhibition of LH release was observed at the dose 100 micrograms of the analog.
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